End-systolic Meridional Stress Research Articles

Effect of NF-κB inhibitor on Toll-like receptor 4 expression in left ventricular myocardium in two-kidney-one-clip hypertensive rats.

To investigate the effects of an inhibitor of NF-κB, PDTC (pyrrolidine dithiocarbamate), on TLR4 (Toll-like receptor 4) expression in the left ventricle of Goldblatt hypertension rats. Goldblatt rat model of two-kidney, one-clip (2K1C) hypertension was established in 70 healthy male rats. The rats were randomly divided into sham operation group (S group, n=20), non-drug intervention hypertension group (H group, n=25), and PDTC intervention group (P group, n=25). P group was injected with PDTC. The clip was inserted in the left renal artery of H group and P group (2K1C). Eight weeks after the operation, the rats were sacrificed and the samples of the left ventricle were collected. The concentration of AngII in the left ventricle was assessed by radioimmunoassay. RT-PCR was used to examine the mRNA expression of TLR4 in the left ventricle. Immunohistochemistry was adopted to examine the location of TLR4 and NF-κB in the myocardium. Victoria blue-Ponceau staining of Cardiac collagen was used to evaluate the degree of myocardial fibrosis. Eight weeks after the operation, caudal SBP, meridional end-systolic stress, left ventricular mass index, relative wall thickness, cardiac fibrosis degree, and the concentration of AngII in the left ventricle in P group were significantly lower than those in H group (p<0.01). In cardiac myocytes of S group and P group, TLR4 expression was diffused and presumably cytoplasmic. TLR4 mRNA expression in P group was significantly lower than that of H group (p<0.01). PDTC not only inhibited the activation of NF-κB, but decreased TLR4 expression and AngII content, indicating that the inflammatory signals and oxidative stress mediated by TLR4/NF-κB are involved in the occurrence and development of left ventricular remodeling. Intervention with TLR4/NF-κB and anti-inflammatory and anti-oxidative therapy may be a new target to reverse left ventricular remodeling.

Insulin-Like Growth Factor 1 (IGF- 1) Levels And Left Ventricular Meridional End Systolic Stress (LVMESS) Interrelationship In Middle- Aged And Elderly Obese Subject With Type 2 Diabetes Mellitus

Background: Left ventricular meridional end systolic stress (LVMESS) is a quantitative determinant index of LV afterload which is an essential determinant of LV performance. The key factors influencing LVMSS, notably ventricular wall thickness, chamber size and configuration are shown to be altered by both obesity and type2 diabetes mellitus (T2DM). There exist reports implicating high free insulin-like growth factor 1 (IGF-1) but not growth hormone (GH) levels, with increased left ventricular mass index (LVMI), abnormal LV geometric remodeling, and A1c levels. Objective: to explore whether a meaningful link exists between LVMESS and free IGF-1 plasma levels, in obese middle-aged and elderly individuals with or without T2DM. Methodology: In this cross sectional study, a total of 145 participants Involved. Middle aged and elderly obese individuals with or without T2 DM were matched with healthy lean subjects of the same age group, with or without T2 DM. LVMESS and IGF-1 levels were compared between groups; group differences were analyzed using unpaired t test and linear correlation test. Data were expressed as the mean ± S.D, using SPSS version 18). Results: LVMESS values showed significant decrease in diabetic patients compared to control in both middle and old aged subjects. IGF-1, concentration levels were lower in the elderly obese diabetics compared to control, with significant (r=0.462; p= 0.04) negative correlation with LVMESS in healthy obese old aged, and a negative but non-significant correlation with LVMESS in lean old aged with or without diabetics Conclusion: Nonlinear correlation of IGF-1 levels with LVMESS obtained. It could be hypothesized that because of its negative significant correlation with LVMESS in the elderly non diabetic obese, IGF-1 free level could be utilized to serve as a predictor of impaired LV systolic function in these subjects. In addition the results could shed some light on IGF-1- LVMESS relationship, when considering IGF-1 therapy in certain conditions. Recommendation: It is suggested that using IGF-1 plasma levels in the elderly with or without T2DM could aid as predictor for LV global systolic dysfunction .However, larger sample size are to be considered.

A randomized placebo controlled double blind crossover study of pioglitazone on left ventricular diastolic function in type 2 diabetes

Background/ObjectivesThiazolidinediones (TZDs), such as pioglitazone, are widely used to treat type 2 diabetes but there is evidence that their use is associated with an increased risk of heart failure. We compared the effect of pioglitazone vs. placebo on left ventricular (LV) diastolic and systolic function in people with type 2 diabetes. Methods and results24 male or female patients with type 2 diabetes were randomized to pioglitazone (45mg/day) or placebo in addition to current therapy for 12weeks using a prospective double blind crossover protocol following a run-in period >1week and a 2week washout period at crossover. Tissue Doppler early peak velocity (e′), a measure of LV diastolic function, was the primary outcome. Pioglitazone significantly increased e′ by 0.7(0.1, 1.3) cm/s (mean (95% confidence interval); p=0.02) compared with placebo. Pioglitazone also increased E/A and mitral deceleration index, ejection fraction, stroke volume and weight, whereas fasting glucose, HbA1c, total peripheral resistance and LV meridional end systolic stress were decreased. ConclusionsTreatment with pioglitazone for 12weeks improves left ventricular diastolic and systolic function in people with type 2 diabetes.

Acute improvement in arterial-ventricular coupling after transcatheter aortic valve implantation (CoreValve) in patients with symptomatic aortic stenosis

The recent development of transcatheter aortic valve implantation (TAVI) to treat severe aortic stenosis (AS) offers a viable option for high-risk patients categories. Our aim is to evaluate the early effects of implantation of CoreValve aortic valve prosthesis on arterial-ventricular coupling by two dimensional echocardiography. Sixty five patients with severe AS performed 2D conventional echocardiography before, immediately after TAVI, at discharge (mean age: 82.6 ± 5.9 years; female: 60%). The current third generation (18-F) CoreValve Revalving system (Medtronic, Minneapolis, MN) was used in all cases. Vascular access was obtained by percutaneous approach through the common femoral artery; the procedure was performed with the patient under local anesthesia. We calculated, apart the conventional parameters regarding left ventricular geometry and the Doppler parameters of aortic flow (valvular load), the vascular load and the global left ventricular hemodynamic load. After TAVI we showed, by echocardiography, an improvement of valvular load. In particular we observed an immediate reduction of transaortic peak pressure gradient (P < 0.0001), of mean pressure gradient (P < 0.0001) and a concomitant increase in aortic valve area (AVA) (0.97 ± 0.3 cm(2)). Left ventricular ejection fraction improved early after TAVI (before: 47 ± 11, after: 54 ± 11; P < .0001). Vascular load, expressed by systemic arterial compliance, showed a low but significant improvement after procedure (P < 0.01), while systemic vascular resistances showed a significant reduction after procedure (P < 0.001). As a global effect of the integrated changes of these hemodynamic parameters, we observed a significant improvement of global left ventricular hemodynamic load, in particular through a significant reduction of end-systolic meridional stress (before: 80 ± 34 and after: 55 ± 29, P < 0.0001). The arterial-valvular impedance showed a significant reduction (before: 7.6 ± 2 vs after: 5.8 ± 2; P < 0.0001. Furthermore we observed a significant reduction with a normalization of arterial-ventricular coupling (P < 0.005). With regard to left ventricular (LV) efficiency, we observed, after the procedure, a significant reduction of stroke work (P < 0.001) and potential energy (P < 0.001), with a significant increase of work efficiency early after the procedure (P < 0.001). Our results showed that the TAVI procedure was able to determine an early improvement of the global left ventricular hemodynamic load, allowing a better global LV performance. Further follow-up investigations are needed to evaluate these results in a more prolonged time observation.

Differences of myocardial systolic deformation and correlates of diastolic function in competitive rowers and young hypertensives: a speckle-tracking echocardiography study

The aim of this study was to compare speckle-tracking echocardiography–derived left ventricular (LV) systolic mechanics and their relationships with LV diastolic properties in young patients with hypertension and in young competitive athletes in relation to their respective alterations of LV structure. Nineteen sedentary controls, 22 top-level rowers, and 18 young newly diagnosed, never-treated patients with hypertension, all male, underwent Doppler echocardiography including pulsed tissue Doppler of the mitral annulus and speckle-tracking echocardiography. Peak longitudinal strain was calculated in apical long-axis, four-chamber, and two-chamber views, and values of the three views were averaged (global longitudinal strain [GLS]). Regional circumferential and radial strain were calculated at the LV basal, middle, and apical levels, and values were averaged. LV torsion was determined as the net difference in the mean rotation between the apical and basal levels. The three groups were comparable for age, whereas body mass index and blood pressure were higher in patients with hypertension, and heart rate was lower in rowers. LV mass index was higher in rowers and in patients with hypertension than in controls, without differences in relative wall thickness, ejection fraction, and midwall shortening. Left atrial volume index was greater in rowers than in controls and patients with hypertension. Annular systolic velocity (s0) (P < .001) and early diastolic velocity (e0) (P < .0001) were lower and the E/e0 ratio was higher (P < .0001) in patients with hypertension. GLS was lower in patients with hypertension than in rowers and in controls (P < .0001). Global circumferential strain, global radial strain, and torsion were similar among the three groups. In the pooled population, GLS was an independent contributor to E/e0 ratio (P < .0001) after adjusting for age, heart rate, meridional end-systolic stress, LV mass index and left atrial volume index. By receiver operating characteristic curve analyses, both GLS and E/e0 ratio appeared to be accurate in discriminating patients with hypertension from healthy controls, with the E/e0 ratio being more sensitive (77.8%) and GLS more specific (89.5%). The hearts of young patients with hypertension are characterized by reduced GLS, whereas global circumferential strain, global radial strain, and torsion are similar to those of athletes’ hearts. The extent of GLS is strongly associated with LV diastolic function, independently of afterload changes and the degree of LV hypertrophy.

Differences of Myocardial Systolic Deformation and Correlates of Diastolic Function in Competitive Rowers and Young Hypertensives: A Speckle-Tracking Echocardiography Study

The aim of this study was to compare speckle-tracking echocardiography-derived left ventricular (LV) systolic mechanics and their relationships with LV diastolic properties in young patients with hypertension and in young competitive athletes in relation to their respective alterations of LV structure. Nineteen sedentary controls, 22 top-level rowers, and 18 young newly diagnosed, never-treated patients with hypertension, all male, underwent Doppler echocardiography including pulsed tissue Doppler of the mitral annulus and speckle-tracking echocardiography. Peak longitudinal strain was calculated in apical long-axis, four-chamber, and two-chamber views, and values of the three views were averaged (global longitudinal strain [GLS]). Regional circumferential and radial strain were calculated at the LV basal, middle, and apical levels, and values were averaged (global circumferential strain and global radial strain). LV torsion was determined as the net difference in the mean rotation between the apical and basal levels. The three groups were comparable for age, whereas body mass index and blood pressure were higher in patients with hypertension, and heart rate was lower in rowers. LV mass index was higher in rowers and in patients with hypertension than in controls, without differences in relative wall thickness, ejection fraction, and midwall shortening. Left atrial volume index was greater in rowers than in controls and patients with hypertension. Annular systolic velocity (s') (P < .001) and early diastolic velocity (e') (P < .0001) were lower and the E/e' ratio was higher (P < .0001) in patients with hypertension. GLS was lower in patients with hypertension (-17.5 ± 2.8%) than in rowers (-22.2 ± 2.7%) and in controls (-21.1 ± 2.0%) (P < .0001). Global circumferential strain, global radial strain, and torsion were similar among the three groups. In the pooled population, GLS was an independent contributor to E/e' ratio (P < .0001) after adjusting for age, heart rate, meridional end-systolic stress, LV mass index and left atrial volume index. By receiver operating characteristic curve analyses, both GLS and E/e' ratio appeared to be accurate in discriminating patients with hypertension from healthy controls, with the E/e' ratio being more sensitive (77.8%) and GLS more specific (89.5%). The hearts of young patients with hypertension are characterized by reduced GLS, whereas global circumferential strain, global radial strain, and torsion are similar to those of athletes' hearts. The extent of GLS is strongly associated with LV diastolic function, independently of afterload changes and the degree of LV hypertrophy.

Assessment of longitudinal left ventricular systolic function by different echocardiographic modalities in patients with newly diagnosed mild-to-moderate hypertension

Standard echocardiographic methods reflect chamber dynamics and do not provide a direct measure of myocardial fiber shortening. Therefore we evaluated longitudinal left ventricular myocardial function by tissue Doppler echocardiography; strain (S), strain rate (SR), tissue Doppler velocity (TDV) in newly diagnosed mild to moderate hypertensive patients. Our cross-sectional and observational study population consisted of 57 patients and 48 normotensive control subjects. Patients with obesity, diabetes mellitus, regional wall motion abnormality, secondary hypertension and a history or clinical evidence of cardiovascular disease, arrhythmias or conduction abnormalities were excluded from the study. Ejection fraction, endocardial fractional shortening (eFS), meridional end-systolic stress (mESS), stress-adjusted eFS (observed /predicted eFS) were measured by M-mode echocardiography. Relationship between the left ventricular mass index and mESS was assessed by Pearson's linear regression model. Hypertensive patients had significantly decreased longitudinal myocardial function compared to control subjects determined by septal (-1.25+/-0.30 vs. -1.02+/-0.33, p<0.001) and lateral (-1.20+/-0.28 vs. 1.02+/-0.41, p<0.01) SR (1/s) measurements. However, there was no significant correlation between the mESS and strain-strain rate measurements in both normal and hypertensive subjects. Early impairment in longitudinal left ventricular systolic function can be expected despite normal endocardial left ventricular function indicated by M-mode echocardiography in patients with newly diagnosed and never treated mild to moderate hypertension.

Impact of Diabetes on the Left Ventricular Long Axis and Midwall Function in Patients with Hypertension

Diabetes mellitus (DM) is a strong risk factor for cardiovascular morbidity and mortality. It is suggested that both hypertension and DM may synergistically affect left ventricular (LV) structure and function. To assess whether hypertensive patients with DM have more depressed LV function in terms of long axis and midwall function by use of tissue Doppler echocardiogram than do patients with hypertension only. Hypertensive patients (n=200) and hypertensive patients with DM (n=60), all of whom had normal LV ejection fraction, were recruited for the study. Healthy age- and sex-matched subjects (n=20) served as the control group. Echocardiography was performed including LV wall thickness, dimension, Doppler, and tissue Doppler imaging. Blood pressure (BP) was measured in the supine position before and after echocardiographic examination. The hypertensive patients with or without DM had higher BP and LV wall thickness, had more decreased afterload measured by meridional end-systolic stress, and had more depressed LV diastolic, long axis, and global function than did the controls. There was no difference in LV function between the hypertensive patients with and without DM. The hypertensive patients with or without DM had depressed LV function compared with the controls, but there was no difference between the hypertensive patients with or without DM. DM does not seem to have additive adverse effects on the LV long axis and midwall function in persons with hypertension.

Left ventricular remodeling, mechanics, and tissue characterization in congenital aortic stenosis

Background: As the response of the myocardium to pressure overload is age-dependent, this study was designed to examine left ventricular (LV) remodeling, mechanics, and tissue characterization in children with moderate congenital aortic stenosis. Methods: We studied by echocardiography Doppler 22 patients (mean age 12.4 ± 5.6 years) with peak and mean transvalvular gradient of 63 ± 6 and 32 ± 4 mm Hg, respectively. In addition, 30 age- and body surface area-matched participants with structurally normal hearts were used as a control group. Sex- and age-specific cut-off levels for LV mass/height2.7 and relative wall thickness were defined to assess LV geometry. As a load-independent index of myocardial contractility, the relation between the rate-corrected velocity of circumferential fiber shortening both at endocardium and midwall, and meridional end-systolic stress was assessed. In addition, LV diastolic function was also evaluated by the mitral flow indexes. Finally, ultrasonic tissue characterization of the LV myocardium was performed by calculating the magnitude of cyclic variation, which reflects the intramural contractile function, and the averaged myocardial intensity of integrated backscatter, which is directly related to the myocardium collagen content. Results: The endocardial velocity of circumferential fiber shortening endocardium and meridional end-systolic stress relationship was within the normal range (mean ± 2SD) in 18 of 22 patients (81.8%), and midwall velocity of circumferential fiber shortening at endocardium and meridional end-systolic stress was normal in all 22 patients. No mitral flow index of LV diastolic function was significantly different between aortic stenosis group and normal participants. In our study population, 16 of 22 patients (72.7%) showed normal LV geometry, 3 (13.6%) had a pattern of concentric remodeling, and 3 (13.6%) concentric hypertrophy. LV hypertrophy was not marked (left ventricular mass index [LVMI] < 51 g/m2.7) in any patient. Finally, compared with control participants our study population showed, both at interventricular septum and posterior wall, comparable values of cyclic variation integrated backscatter, but significantly higher values of averaged myocardial integrated backscatter intensity (P <.01). Conclusions: In children with moderate congenital aortic stenosis, the total amount of myocardial collagen was increased despite normal LV myocardial contractility and diastolic function. Furthermore, LV remodeling was abnormal in only about a quarter of our patients and none had more than mild hypertrophy. Although the majority of these patients do not have markers now recognized to predict higher risk of cardiovascular events, the long-term significance of myocardial fibrosis and its response to treatment remain to be investigated. (J Am Soc Echocardiogr 2003;16:214-20.)

Left ventricular mass and hemodynamic overload in normotensive hemodialysis patients

It remains uncertain whether the hemodynamic parameters are important determinants of left ventricular mass (LVM) in normotensive chronic hemodialysis (NTHD) patients, as has been found in their hypertensive counterparts. Forty NTHD patients (mean age, 53.7 +/- 14.4 years; male/female, 18/22) without the requirement of antihypertensive drugs for at least six months were studied. Controls were 41 hypertensive hemodialysis patients (HTHD) and 46 normotensive subjects with normal renal function (NTNR). The influence of anthropometrics, cardiovascular structure and function, and volume status on LVM (by two-dimensional echocardiography) was analyzed by steps of multiple linear regression. As compared with the NTNR and NTHD group, the HTHD group had obvious pressure and volume/flow overload, and greater LV wall thickness, chamber size and mass. In contrast, NTHD subjects had similar blood pressure, large artery function, LV chamber size and stroke volume as the NTNR subjects. However, the NTHD patients still had greater wall thickness and LVM, along with greater cardiac output, lower total peripheral resistance and lower end-systolic meridional stress to volume ratio (ESSV) than the NTNR group. LVM in the NTHD group was significantly positively related to averaged systolic blood pressure (SBPavg), body surface area, extracellular fluid (ECF), carotid intima-media thickness (IMT), aortic pulse wave velocity (PWV), and negatively related to ESSV and Kt/V. The independent significant noncardiac structural determinants of LVM in NTHD subjects were ESSV, SBPavg, PWV and SV (model r2 = 0.617, P < 0.001). The NTHD patients, without significant pressure and volume overload, still had increased LVM that was partially explained by the persistent flow overload and subclinical LV dysfunction.

Wall tension or stress in ischemic heart disease

Wall stress or wall tension is a conception derived from physics (Laplace's law) and represents the systolic force or work per surface unit. It is the systolic force made by myocardial tissues. Stress increase indicates enlargement of the left ventricle or increase of intracavitary pressure. This investigation included 170 subjects; control group consisted of 50 patients (pts) with normal coronary angiographic finding without valvular anomalies and the examination group included 120 pts with coronary disease. Transthoracic echocardiography was performed in the left lateral position using computerized Hewlett Packard SONOS 1000 apparatus. Invasive hemodynamic procedure was performed using GENERAL ELETRICS CGR 300. Meridional and equatorial systolic and diastolic stress were calculated according to Grossman formula. The meridional end-diastolic equatorial stress was 18.55 +/- 12.12 dyn/cm2 x 10(3) in the control group, while in coronary patients it was 28.15 +/- 13.42 dyn/cm2 x 10(3). In healthy persons the meridional end-systolic stress established by echocardiography was 190.37 +/- 23.15 dyn/cm2 x 10(3), while in coronary patients 203.82 +/- 17.88 dyn/cm2 x 10(3). End-diastolic equatorial stress was 34.32 +/- 17.18 dyn/cm2 x 10(3) in the control group and 46.13 +/- 17.82 dyn/cm2 x 10(3) in coronary patients. Systolic equatorial stress in the control group was 357.42 +/- 32.15 dyn/cm2 x 10(3) and in coronary patients 385.34 +/- 35.72 dyn/cm2 x 10(3). The same parameters determined by invasive hemodynamic procedure were slightly higher, but without statistical significance in relation to the values determined by echocardiography (P > 0.05). Values of equatorial and particularly meridional stress were higher in coronary patients in relations to healthy persons, but without significant difference. The correlation coefficients of all investigated parameters established by noninvasive 2D echocardiography and invasive hemodynamic procedure were in one domain of medium high and high values. Meridional stress increases in coronary patients, equatorial in hypertensive patients or valvular anomalies with severe myocardial hypertrophy. In regard to high correlation between these two techniques, echocardiography may be considered a highly reliable method in evaluation of wall tension.

Cardiac Performance in Turner’s Syndrome Patients on Growth Hormone Therapy

Objectives: To investigate possible cardiac morphofunctional alterations observed in 26 Turner’s syndrome (TS) patients on prolonged high-dose growth hormone (GH) therapy. Study Design: We examined 26 TS subjects treated with rhGH (1 U/kg/week) for a mean period of 4.9 years (range 1–7.8) and 37 age-, weight- and height-matched healthy girls. Left ventricular volume, mass, systolic function, cardiac index, systemic vascular resistance and diastolic function were evaluated by two-dimensional and Doppler echocardiography. Results: Heart rate and systolic blood pressure (BP) were higher in TS patients than in controls, while diastolic BP was lower. Left ventricular volumes, ejection fraction, mass index, M/V ratio and cardiac index did not differ significantly; systemic vascular resistance was slightly decreased. Left ventricular fractional shortening and mean velocity of circumferential shortening were slightly increased while end-systolic meridional stress was decreased in TS. Contractile state was normal in TS. Diastolic function assessment showed a shortening of isovolumetric relaxation and diastolic filling times with an increased atrial contribution and a normal pulmonary venous flow. Conclusion: Cardiac morphology in TS patients on GH therapy is similar to controls. The observed changes in left ventricular systolic and diastolic function should be interpreted as an adaptation to the higher heart rate and reduced peripheral vascular resistance induced by GH therapy.

Age-related variation in left ventricular myocardial contractile state expressed by the stress velocity relation.

The assessment of ventricular function plays an important role in the pre- and postoperative management of many congenital heart abnormalities. Normal ranges in left ventricular systolic function indices have been defined during childhood and age-related alterations in left ventricular myocardial contractile state have recently been reported. This study was carried out to investigate the developmental changes in left ventricular contractile state expressed by the endsystolic meridional stress (ESS)/rate-corrected velocity of circumferential fiber shortening (VCFc) relation, calculated by echo in normal children and young adults. We examined 146 healthy subjects (80 males and 66 females), mean age 70.85 +/- 63.89 months (range 0.5-228) and body surface area (BSA) 0.807 +/- 0. 47 (range 0.18-2.01) with no clinical and echocardiographic evidence of cardiac disease and with normal blood pressure. The subjects were divided into three groups according to age: <6 months (group 1, n = 32), 6-36 months (group 2, n = 34), and >36 months (group 3, n = 80). Enddiastolic volume and mass (M) of the left ventricle were measured by M-mode Echo. ESS was considered as an index of afterload and the VCFc as an index of systolic ventricular function. The left ventricular ejection time used for the calculation of VCFc was measured from aortic flow obtained by PW-Doppler. The ESS/VCFc relation was used to assess left ventricular contractility. Systolic blood pressure, volume, and mass of the left ventricle increase with age. The gradual increase in pressure despite a stable mass/volume ratio [M/V = 0.900 + (0.0007 x age); r = 0.27, p < 0.005] resulted in a substantial increase of afterload [ESS = 29.78 + (0.116 x age); r = 0.58, p < 0.0001]. VCFc showed an inverse hyperbolic regression with afterload [VCFc = 1.01 + (7.598/ESS); r = 0.59, p < 0.0001]. The regression lines (best linear fit) between VCFc and ESS are significantly different in the three groups. The Y intercept was higher and the slope steeper in group 1 [VCFc = 1.74 - (0.017 x ESS); r = 0.65, p < 0.0005] vs group 2 [VCFc = 1.54 - (0.008 x ESS); r = 0.58, p < 0.001] and group 3 [VCFc = 1.52 - (0.007 x ESS); r = 0.57, p < 0.0001]. These data indicate that, in children, the volume and mass of the left ventricle increase, whereas the M/V ratio remains relatively constant; the progressive increase in arterial blood pressure explains the increase of afterload. The VCFc is higher in the first few years of life compared to that seen in older children due to reduced afterload and increased contractile state. Left ventricular contractility, expressed as ESS/VCFc relation, is thus inversely proportional to age. In the first months of life the left ventricular myocardium exhibits a higher basal contractile state and a greater sensitivity to changes in afterload. For obtaining an accurate assessment of left ventricular function, the ESS/VCFc relation in different age groups should be measured.

Cardiovascular effects of high-dose growth hormone treatment in growth hormone-deficient children.

Growth hormone (GH) hypersecretion is associated with an increased incidence of cardiac hypertrophy and subclinical abnormalities of left ventricular (LV) function. The unlimited availability of biosynthetic GH has led to progressively increased dosage when treating GH-deficient children, raising the question of its cardiovascular effects during long-term therapy. We compared 22 children (8 girls, 14 boys), mean age 12.1 years (range 3-17 years) with GH deficiency who were receiving chronic GH treatment (GH group) with 22 normal controls matched for sex and body size in order to evaluate: (1) LV volume, mass, and systolic function by two-dimensional guided M-mode echocardiography; (2) LV diastolic function by pulsed-wave Doppler sampling of the transmitral flow; and (3) cardiac output and systemic vascular resistance by Doppler echocardiography. All patients had been on chronic GH therapy for 13.8 +/- 7.6 months (range 5-30 months) with an average dose of 0.95 +/- 0.12 IU/kg per week (range 0.69-1.17 IU/kg per week). Blood pressure did not differ between the two groups. LV volume, mass, ejection fraction, and mean velocity of circumferential shortening did not differ significantly between the GH group and controls; nor did the peak- and end-systolic meridional stress. All patients had a normal contractile state as estimated by the relation between mean velocity of circumferential shortening and end-systolic meridional stress. The LV filling parameters did not differ between the two groups, and there was no difference in cardiac index and systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of Fontan operation on left ventricular size and contractility in tricuspid atresia.

Left ventricular dimensions and contractility were determined by echocardiography in 33 patients with tricuspid atresia in 1985 and again in 1988. Eight patients remained palliated throughout the 3-year period; neither the left ventricular end-diastolic diameter (153 +/- 15% of normal vs. 157 +/- 19%, p = NS) nor a load-independent index of contractility (rate-corrected velocity of shortening [VCFc]/end-systolic meridional stress [ESSM]) changed. Eleven patients underwent a Fontan operation during the study and were reevaluated at least 6 months after surgery; left ventricular dimension decreased (130 +/- 15% vs. 114 +/- 19%, p less than 0.001), and the contractility index VCFc/ESSM improved (p less than 0.05). Fourteen patients had undergone a Fontan operation 0.9-9.5 years (mean, 4.2 years) before initial examination in 1985. Over the 3-year period, left ventricular dimensions did not change (121 +/- 17% vs. 118 +/- 11%, p = NS), but the contractility index showed significant improvement (p less than 0.01). Eight additional patients were studied just before and after a Fontan operation to examine the early effects of surgery. Left ventricular dimensions decreased from 130 +/- 14% to 100 +/- 13% by 10 days p less than 0.001) with no further change at 2 months. An inappropriate degree of ventricular hypertrophy was observed in only the early postoperative period. Successful Fontan repair results in rapid reduction of left ventricular size, followed by regression of hypertrophy to a normal mass-to-volume ratio. Operating at more favorable dimensions and loading conditions results in an early increase in left ventricular contractility, which further improves in the medium term follow-up.

Left ventricular function from end-systolic stress-shortening relations in mitral valve prolapse.

Left ventricular (LV) function was studied from end-systolic stress-shortening relations in 13 patients with mitral valve prolapse (MVP). Studies were made noninvasively using M-mode echocardiography with blood pressure measurements on the right arm from a Baumanometer cuff. Fifteen age and sex-matched normal subjects formed the control group. LV end-diastolic dimension was normal in MVP, while shortening fraction (p less than 0.05) and velocity of circumferential fiber shortening (mean Vcf) in the short axis of the ventricle were increased (p less than 0.05). Ventricular afterload, as measured by meridional end-systolic stress was reduced in MVP (p less than 0.01) but the slope of the stress-shortening curve was not different form normal. The decrease in end-systolic stress was related to the severity of prolapse (r = 0.63, p less than 0.05). The study implied that mid- or basal LV contractility was normal in MVP. The increased shortening fraction of the LV minor axis was in keeping with geometrical changes and a reduced ventricular afterload.

Effects of six-month afterload reduction therapy with hydralazine in chronic aortic regurgitation

Seventeen patients with chronic asymptomatic aortic regurgitation (AR) were studied to determine whether 6 months of hydralazine therapy can reduce the severity of AR or reverse left ventricular (LV) enlargement and hypertrophy. Echocardiography, radionuclide angiography at rest and during exercise, and maximal treadmill exercise with respiratory gas analysis were performed at intake and after a 6-month double-blind treatment period. After dose titration with hydralazine, patients were randomized to their maximal tolerated hydralazine dose or to placebo. At intake, hydralazine and placebo groups were similar. Six patients taking hydralazine and 8 taking placebo completed the study protocol. One patient taking placebo died and 2 patients taking hydralazine withdrew with drug-related adverse effects. The mean titrated dose of hydralazine was 93 ± 9 mg, but the mean treatment dose was 63 ± 21 mg administered 3 times daily because of drug intolerance. After 6 months, mean systolic blood pressure with hydralazine therapy decreased from 136 to 125 mm Hg (p < 0.02), and end-systolic posterior wall thickness increased from 1.58 to 1.70 cm (p < 0.05), resulting in a significant reduction in M-mode meridional end-systolic stress (from 104 to 80 kdynes/cm 2) (p < 0.05). M-mode fractional shortening increased from 0.28 to 0.31 (p < 0.05) with hydralazine, but mean LV echocardiographic dimensions were unchanged. LV mass increased from 383 to 434 g (p < 0.05) with hydralazine primarily because of an increase In end-diastolic wall thickness. In the placebo group, there was no change in any of the hemodynamic or echocardiographic parameters at 6 months. Treadmill exercise variables, radionuclide ejection fraction and regurgitant fraction at rest were unchanged in either group at 6 months; however, in patients taking hydralazine, the ejection fraction during exercise increased from 64 ± 12 to 72 ± 9% (p < 0.02). It is concluded that 6 months of hydralazine therapy in maximal tolerated doses does not alter the severity of regurgitation or reduce LV enlargement and hypertrophy in chronic severe AR, although systolic function may be improved.

Mechanics of pulsus alternans in aortic valve stenosis

Differences in the mechanics of strong and weak contractions during sustained pulsus atternans were studied in 4 patients with aortic valve stenosis (AS). No significant difference was observed between strong (S) and weak (W) beats in M-mode echographic end-diastolic minor-axis dimension or end-diastolic meridional wall stress. Peak systolic meridional stress (S:225 × 10 3 dynes/cm 2; W:205 × 10 3 dynes/cm 2), the time integral of left ventricular (LV) meridional systolic stress (S:5,000 × 10 3 dynes/cm 2; W:4,500 × 10 3 dynes/cm 2) and the area of a stress dimension loop (S:202 × 10 3 dyne/cm; W 165 × 10 3 dyne/cm) were all greater for strong beats. However, end-systolic meridional stress (S: 100 × 10 3 dynes/cm 2; W:115 × 10 3 dynes/cm 2) and end-systolic minor-axis dimension (S:4.75 cm; W:5.0 cm) were significantly greater for weak beats. Stress-length relations, derived from resting and postnitroglycerin determinations, revealed higher end-systolic dimensions for weak beats at any level of limiting afterload, suggesting diminished contractile performance of weak beats. Additionally, fractional minor-axis shortening for weak beats was diminished, at any level of end-systolic stress, in comparison with that for strong beats. The results are supportive of theories suggesting alternating contractile performance during pulsus alternans.