Left ventricular diastolic function abnormalities in hypopituitary patients with GH deficiency: evidence for a subclinical cardiomyopathy

The aim of this study was to evaluate cardiac performance, in particular diastolic function, in adult patients with adulthood onset GH deficiency. The study group was composed of 19 GH deficient adult hypopituitary patients with at-least 3 additional pituitary hormone deficits and 19 age, sex and BMI matched healthy controls. Mean duration of hypopituitarism was 108.6 +/- 77.0 months. None of the patients and controls presented with or had previous diagnosis of concomitant diseases that could affect cardiac function. All hormone deficiencies, except for GH, were appropriately replaced in the patients. Left ventricular function and geometry were evaluated by two-dimensional, M-mode and Doppler echocardiography. Body composition was evaluated by bioelectrical impedance analysis. Not significant differences were observed with respect to left heart dimensions and left ventricular systolic function between patients and controls. Nevertheless 2 of the left ventricular diastolic function parameters, deceleration time and isovolumetric relaxation time, were significantly prolonged in the patients compared with controls (247.88 +/- 70.65 vs 143.26 +/- 31.70 milliseconds (ms) and 122.31 +/- 18.24 vs 89.47 +/- 12.12 ms respectively, p<0.001). Duration of hypopituitarism was significantly correlated with percent body fat mass (r=0.6119, p<0.01) and percent lean body mass (r=-0.5949, p<0.01). It is concluded that in adults affected by hypopituitarism, GH deficiency predominantly impairs diastolic function while systolic function at rest is spared. This observation might indicate a preclinical stage of a cardiomyopathy.     

Cardiovascular consequences of early-onset growth hormone excess

Acromegaly has relevant effects on the cardiovascular system, but few data deal with the early effects of GH and IGF-I excess. To study the early stage of acromegalic cardiomyopathy and give indirect evidence of the mechanisms underlying GH and IGF-I action on the human heart, 25 patients with uncomplicated acromegaly [15 young subjects with short-term (< or =5 yr) disease and 10 with long-term (>5 yr) disease] and 25 sex- and age-matched controls were studied. Cardiovascular risk parameters were studied by standard methods; cardiac morphology by M-mode and Doppler echocardiography, cardiac function at rest and at peak exercise by equilibrium radionuclide angiography, and vascular disease at common carotid arteries by Doppler ultrasonography. In the patient group these measurements were repeated after 6 months of treatment with octreotide-LAR (20-40 mg, im, every 28 d). Glucose, glycosylated hemoglobin, insulin, low density lipoprotein cholesterol, triglycerides, and fibrinogen levels were higher, and high density lipoprotein cholesterol levels were lower in acromegalic patients than in controls. Resting blood pressure was similar in patients and controls, whereas heart rate at rest and systolic blood pressure at peak exercise were higher in the patients. The left ventricular mass index was higher in acromegalic patients than in controls (123.3 +/- 8.9 vs. 81.5 +/- 4.3 g/m(2); P < 0.001); seven patients had left ventricular hypertrophy. Diastolic function was similar in the two groups. The ejection fraction at rest, but not at peak exercise, was significantly increased in the patients compared with controls. As a consequence the exercise-induced changes in the ejection fraction were lower in patients than controls (8.7 +/- 1.1% vs. 21.9 +/- 3.5%; P < 0.001). At common carotid ultrasonography, young patients with acromegaly had increased diastolic peak velocity and increased intima media thickness, even if neither patient nor controls had atherosclerotic plaques. Six months after OCT-LAR treatment, GH and IGF-I levels remarkably decreased in all patients; 8 (53.3%) achieved disease control. Insulin, total cholesterol, and fibrinogen levels reduced, whereas high density lipoprotein cholesterol levels increased. Both at rest and at peak exercise, heart rate significantly decreased, whereas systolic and diastolic blood pressures did not change. The left ventricular mass index was significantly reduced, but it was still higher than the control value (101.6 +/- 3.5 g/m(2); P < 0.01). The left ventricular ejection fraction at rest was significantly reduced, but its response at peak exercise was increased (16.3 +/- 2.4%), becoming similar to the control value. At common carotids, the intima media thickness of right and left arteries was significantly reduced as was the diastolic peak velocity without any change in systolic peak velocity. Short-term GH excess, despite causing enhanced cardiac performance at rest, reduces cardiac performance on effort and impairs vascular morphology. These deleterious effects of early-onset acromegaly are ameliorated by suppressing GH/IGF-I levels for 6 months.     

The influence of growth hormone (GH) therapy on cardiac performance in patients with childhood onset GH deficiency.

OBJECTIVE: There is accumulating evidence that growth hormone (GH) plays an important role in the maintenance of normal cardiac growth and function. Abnormalities in left ventricular diastolic function and impairment of systolic function have also been reported in patients with GHD. In this study, we investigated the effects of 12 months GH replacement therapy on cardiac functional indices measured by echocardiography, the ECG stress test and SPECT imaging. DESIGN: Sixteen patients with childhood onset GHD (age 42.3+/-13.1 years, 10 males) were investigated before, and after, 12 months of GH treatment at a dosage of 0.02 IU/kg/day (7 microg/kg/day). The GH administration resulted in serum IGF-I levels within the normal range in all the patients. The following investigations were performed initially and after 12 months: electrocardiography, systolic and diastolic blood pressure, heart rate measurement, a complete Doppler-echocardiographic examination, treadmill exercise test and Technetium-99m sestamibi single-photon emission computer tomography (SPECT) imaging at rest and after exercise. RESULTS: Echocardiography showed improvement in left ventricular systolic function after GH treatment. End-systolic volume fell from 29.9+/-12.4 to 24.4+/-6.9 ml (p<0.05) and the ejection fraction increased from 56.2+/-7.2% to 63.2+/-6,1% (p<0.01). Left ventricular diameter and wall thickness did not change after GH treatment, although systolic increase in interventricular septum thickness (IVS%) and systolic increase in posterior wall thickness (PWT%) increased significantly (IVS% 52.2+/-31.9% vs. 67.3+/-30.4% and PWT% 48.7+/-20.2% vs. 58.0+/-17.7%, p<0.01, p<0.01, respectively). Contractile function, measured at midwall level, improved as left ventricular midwall fractional shortening (MWS) increased (16.11+/-6.55 vs. 23.30+/-5.89 %, p<0.01) and stress-corrected MWS increased between the examinations performed before and after 12 months of GH treatment (90.97+/-36.66 vs. 133.10+/-32.84 %, p<0.01). Diastolic function did not change, as assessed by early diastolic flow (E), diastolic flow secondary to atrial contraction (A), or the E/A ratio. The LV-mass index did not change significantly after GH treatment (78.4+/-22.1 vs. 81.9+/-21.1g/m(2)). After 12 months of GH treatment the myocardial performance index (MPI) decreased significantly from 0.483+/-0.146 at baseline to 0.410+/-0.086 at the end of the study (p<0.05). There was a trend towards an increase in exercise duration and capacity after GH treatment but the differences did not reach levels of statistical significance. SPECT imaging basally and after 12 months showed normal myocardial perfusion at rest and after exercise in all the patients. In conclusion, GH replacement therapy in adults with GHD demonstrated the beneficial effects on cardiac functions.     

Adults with childhood-onset growth hormone deficiency: effects fo growth harmone treatment on cardiac structure

OBJECTIVES: To evaluate the effects of growth hormone deficiency (GHD) and of growth hormone (GH) therapy on cardiac structure in adults with childhood-onset GHD. SETTING: Out-patient clinic in the Italian Institute for Auxology, Milan. SUBJECTS: Eight adults with childhood-onset GHD and eight healthy controls, matched for sex, age, exercise and body mass index. INTERVENTIONS: Recombinant GH (Saizen Serono, Italy), administered in a conventional dose of 0.5 IU kg-1 week-1 for 6 months. MAIN OUTCOME MEASURES: Cardiac structure parameters, evaluated by two-dimensional, M-mode and Doppler echocardiograms, and stress test, by means of a modified Bruce protocol with a bicycle ergometer, were determined before and after 6 months GH therapy. RESULTS: Before treatment, mean (+/- SE) intraventricular septal thickness (IVST: 7.1 +/- 0.2 mm), LV posterior wall thickness (LVPT: 5.2 +/- 0.1 mm), LV mass (LVM: 94.6 +/- 5.0 g), LV mass index (LVM/body surface area, LVMI: 65.1 +/- 3.0 g m-2) and left ventricular end-diastolic diameter (LVED: 41.4 +/- 0.6 mm) of patients were significantly lower (P < 0.01) than in controls, whilst LV end-systolic diameter (LVES) of patients (25.5 +/- 0.7 mm) was similar to controls (27.5 +/- 0.7). GH treatment significantly (P < 0.01) increased LVPT (6.8 +/- 0.2 mm), LVM (111.6 +/- 4.6 g) and LVMI (80.5 +/- 3.5 g m-2); no significant changes were observed in LVED, LVES and IVST values. The stress test showed a significant improvement of cardiac performance, as demonstrated by the reduction of blood pressure x heart rate product at the same workload (basal: 32,722.5 +/- 897.4 vs. after: 25,574.6 +/- 439.7). CONCLUSIONS: GH plays a role in the maintenance of a normal cardiac structure in adulthood. The present study suggests that GH treatment might be able to improve the cardiac structure of patients with childhood-onset GHD.     

Cardiac mass and function, carotid artery intima-media thickness, and lipoprotein levels in growth hormone-deficient adolescents

The objective of our study was to evaluate whether cardiac mass and function, carotid artery intima-media thickness, and serum lipid and lipoprotein(a) levels are abnormal in adolescents with GH deficiency. Young adults with childhood-onset and adulthood-onset GH deficiency have been found to have a higher cardiovascular risk, as manifested among other factors by reduced left ventricular mass, impaired systolic function, significant increase in arterial intima-media thickness, and dyslipidemia. Twelve adolescents (seven males and five females) with GH deficiency (10 idiopathic and 2 organic), with an age of 14.2 +/- 2.8 yr and a height of 140.6 +/- 17.9 cm (height SD score, -2.6 +/- 0.3), were studied. Six children had received GH in the past but were off therapy for several years, whereas six patients had never been treated with GH. Fasting blood samples were obtained for serum lipids and lipoprotein(a) analysis. Patients underwent transthoracic M-mode and two-dimensional echocardiographic evaluation for measurement of interventricular septal thickness, left ventricular posterior wall thickness, and left ventricular mass, as well as left ventricular ejection fraction at rest and pulmonary venous flow velocities; carotid artery intima-media thickness was measured using high-resolution mode B ultrasound. Seven GH-deficient (GHD) adolescents on GH at the time of the study and 19 healthy adolescents, all comparable for age, pubertal status, height, weight, blood pressure, and pulse, participated in this study as controls. Interventricular septal thickness (6.5 +/- 1.3 vs. 7.0 +/- 1.5 mm), left ventricular posterior wall thickness (7.0 +/- 1.8 vs. 7.5 +/- 2.0 mm), and left ventricular mass after correction for body surface area (71.2 +/- 21.8 vs. 70.7 +/- 18.0 g/m(2)) were similar in untreated GHD patients and healthy controls. Similarly, the left ventricular ejection fraction at rest was similar in untreated GHD subjects and controls (70.0 +/- 0.7 vs. 70.0 +/- 0.6%), as were the pulmonary venous flow velocities (0.54 +/- 0.16 vs. 0.55 +/- 0.10 m/s for diastolic peak velocity; 0.51 +/- 0.16 vs. 0.50 +/- 0.09 m/s for systolic peak velocity; and 0.19 +/- 0.06 vs. 0.19 +/- 0.05 m/s for atrial reversal filling). Carotid artery intima-media thickness (0.60 +/- 0.02 mm and 0.59 +/- 0.02 mm for the right and left carotid arteries, respectively) was also normal in our untreated GHD patients when compared with healthy controls. In addition, all echocardiographic measurements were similar in GHD subjects on or off GH at the time of the study. Low-density lipoprotein cholesterol levels were increased in untreated GHD patients when compared with healthy controls (3.17 +/- 0.70 vs. 2.33 +/- 0.36 mmol/L; P < 0.01), whereas total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations were similar to that of controls. Total cholesterol levels were increased in our untreated GHD adolescents when compared with GHD subjects receiving GH therapy at the time of the study, while low-density lipoprotein cholesterol and triglyceride levels were also elevated, although not significantly. Lipoprotein(a) levels were elevated in untreated GHD adolescents when compared with healthy controls, and untreated GHD subjects had higher lipoprotein(a) concentrations than GH-treated patients. GHD adolescents, regardless of whether or not they received GH therapy, do not seem to show alterations in cardiac mass and function or early atherosclerotic changes. They must, however, be followed carefully because they already present cardiovascular risk factors such as dyslipidemia, which may increase their cardiovascular morbidity over time.     

Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults Preliminary data in a small group of patients

OBJECTIVE  The long-term cardiovascular effects of GH administration in adults are of major clinical importance, given the increasing use of such treatment. We have evaluated long-term cardiovascular effects of recombinant human GH (rhGH) substitution in GH deficient men.
DESIGN  S.c. rhGH 0.5 U/kg/week or placebo was administered in a 6-month double-blind, cross-over study, followed (after a year without substitution) by a 42-month period of open GH substitution.
PATIENTS  We evaluated 7 GH-deficient men serially and compared the results with 21 men matched in terms of age and height.
MEASUREMENTS  Investigations included exercise tests and Doppler-echocardiography to determine exercise capacity and cardiovascular performance.
RESULTS  Heart rate and systolic blood pressure at rest increased with GH substitution to the level of the controls, as did diastolic blood pressure after an initial reduction. Age-adjusted exercise capacity increased during the study and we found no evidence of ischaemic heart disease on exercise ECG. Stroke volume increased with GH substitution, thereby normalizing the initially reduced cardiac index. There was no significant change in left atrial or ventricular internal dimensions, systolic function as measured by fractional shortening, or diastolic function as measured by isovolumic relaxation time and left ventricular filling (A/E ratio). However, a lower atrial emptying index than that seen among controls might indicate some diastolic disturbance and there was a definite increase in left ventricular wall thickness compared with controls (to 25.1±1.5 vs 19.7±0.4 mm, P <0.001).
CONCLUSIONS  We found that GH substitution in GH-deficient adults had a beneficial effect on physical performance and cardiac output. The concomitant increase in left ventricular mass index might be an effect of an excessive substitution dose.     

Left ventricular mass and function in children with GH deficiency before and during 12 months GH replacement therapy

OBJECTIVE: This open, prospective study was designed to evaluate the effect of GH deficiency (GHD) on left ventricular (LV) mass (LVM) and performance, by echocardiography, and on lipid profile during childhood. SUBJECTS: Twelve prepubertal children with GHD (eight boys and four girls) aged 8.1 +/- 1.7 years were studied before and after 6 and 12 months of GH replacement therapy at a dose of GH of 30 micro g/kg/day. Twelve healthy children sex-, height-, weight- and body surface area-matched with the patients, served as controls. METHODS: Echocardiography was performed at study entry and after 12 months both in GHD children and in controls. Only in GHD children, echocardiography was repeated also after 6 months of GH replacement. In all subjects, we measured LV posterior wall thickness (LVPWT), LV end-diastolic diameter (LVEDD), LVM index (LVMi), LV systolic and diastolic function. RESULTS: At study entry, LVPWT (5.3 +/- 0.8 vs. 6.2 +/- 1.1 mm, P < 0.05), LVEDD (34.0 +/- 2.4 vs. 36.7 +/- 2.1 mm, P < 0.007) and LVMi (47.0 +/- 6.9 vs. 59.6 +/- 9.5 g/m2, P < 0.005) were significantly lower in GHD children than in controls. Lipid profile, heart rate, blood pressure, LV systolic function and indices of ventricular filling were similar in patients and controls. After 12 months of GH replacement therapy, LVPWT (6.1 +/- 0.7 mm, P < 0.0005), LVEDD (38.8 +/- 4.3 mm, P < 0.002) and LVMi (71.5 +/- 12.7 g/m2, P < 0.0005) significantly increased in GHD children compared to pretreatment values. In particular, after 12 months of therapy GHD children achieved a normal LVMi when compared to controls (60.7 +/- 8.6, P = ns). LVMi increase was significantly correlated with the increase in IGF-I level (r = 0.49; P < 0.004). LV systolic performance, diastolic filling and blood pressure did not change significantly during GH therapy. After 12 months of treatment, the atherogenic index, measured as total/high-density lipoprotein-cholesterol ratio (2.7 +/- 0.8) was significantly lower than both pretreatment (3.4 +/- 0.3, P < 0.03) and control values (3.8 +/- 1.1, P < 0.04). CONCLUSIONS: GH deficiency in children affects heart morphology, by inducing a significant decrease in cardiac size, but does not modify cardiac function and lipid profile. Twelve months of GH replacement treatment normalizes cardiac mass, and reduces the atherogenic index.     

The Influence of the growth hormone in the profile of blood pressure. Results in adult patients with deficiency in this hormone

INTRODUCTION AND OBJECTIVES: There is an increasing interest in the relationship between the growth hormone (GH) and the heart since the GH has an important inotropic effect and its use has been tested in patients with severe systolic dysfunction. However, cardiovascular diseases are the main cause of increased morbimortality observed in patients with acromegaly. Growth hormone deficiency has been related to different clinical findings depending on the age of onset. Recent studies have demonstrated that GH deficiency in adults is associated with alterations in blood pressure. The aim of our study was to assess the influence of GH in blood pressure. PATIENTS AND METHODS: We studied 14 adult patients with GH deficiency and 15 healthy subjects, matched for sex and age. The diagnosis of GH deficiency was based on GH response to intravenous insulin tolerance test < 5 ng/ml and IGF-1 levels lower than the normal limit for each age group. In all the patients 24-hour Holter blood pressure monitorization was performed in addition to a treadmill test and echographic evaluation. RESULTS: All patients showed normal systolic and diastolic function in the echocardiographic study. Only one patient had an increased left ventricular mass. Blood pressure was lower in the patients than in the control subjects (p < 0.05). Moreover, the difference remained significant when analysis was based on the time of day. However, the patients showed normal blood pressure response to the effort test with a mean increase of 60%. The length of the exercise on the treadmill test was shorter in the subgroup of GH deficient patients. CONCLUSIONS: Lower systolic blood pressure was observed in GH deficiency patients. The patients studied did not show structural heart alterations. Blood pressure and chronotrophic response to the effort test were similar in both groups.     

The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study

Increased cardiovascular morbidity and mortality were reported in GH deficiency (GHD), and GH replacement can ameliorate cardiac abnormalities of adult GHD patients. To test the potential progression of untreated GHD on the cardiovascular risk and cardiac function, cardiovascular risk factors, cardiac size, and performance were prospectively evaluated in 15 GHD patients (age, 18-56 yr) who were treated with recombinant GH at the dose of 0.15-1.0 mg/d, 15 GHD patients (age, 18-56 yr) who refused GH replacement, and 30 healthy subjects (age, 18-53 yr). Electrocardiogram, systolic and diastolic blood pressure, and heart rate measurement, serum IGF-I, total cholesterol, low- and high-density lipoprotein (LDL, HDL) cholesterol, triglycerides, and fibrinogen level assay, echocardiography, and equilibrium radionuclide angiography were performed basally and after 12 months. At study entry, low IGF-I levels, unfavorable lipid profile, and inadequate cardiac and physical performance were found in GHD patients compared with controls. After 12 months of GH treatment, IGF-I levels normalized; HDL-cholesterol levels, left ventricular (LV) mass index (LVMi), left ventricular ejection fraction (LVEF) at peak exercise, peak filling rate, exercise duration and capacity significantly increased; total- and LDL-cholesterol levels significantly decreased. After 12 months in GH-untreated GHD patients, IGF-I levels remained stable, and HDL-cholesterol levels, LVEF both at rest and at peak exercise, and exercise capacity were further reduced; total- and LDL-cholesterol levels increased slightly. LVEF at rest and its response at peak exercise normalized in 60 and 53.3%, respectively, of GH-treated patients and in none of the GH-untreated patients. In conclusion, 12 months of GH replacement normalized IGF-I and improved lipid profile and cardiac performance in adult GHD patients. A similar period of GH deprivation induced a further impairment of lipid profile and cardiac performance. This finding strongly supports the need of GH replacement in adult GHD patients.     

Increased response of diastolic blood pressure to exercise in patients with coronary artery disease: an index of latent ventricular dysfunction?

OBJECTIVE--To determine whether an abnormal response of diastolic blood pressure during treadmill exercise stress testing correlated with the number of obstructed vessels and with left ventricular systolic function in patients with coronary artery disease. DESIGN--Diastolic blood pressure was measured invasively during exercise stress testing and coronary angiograms and left ventriculograms were obtained at rest in patients with coronary artery disease. The abnormal (> or = 15 mm Hg) diastolic blood pressure response was compared with the number of obstructed coronary arteries and with left ventricular systolic function. SETTING--Two tertiary referral centres. PATIENTS--50 consecutive patients (mean age 57 years) with coronary artery disease. MAIN OUTCOME MEASURES--The increase in diastolic blood pressure during exercise and its correlation with the appearance and disappearance of ST segment deviation, resting left ventricular systolic function, and the number of obstructed coronary arteries. RESULTS--Group 1: 10 (20%) patients (three with one, four with two, and three with three vessel coronary artery disease) (mean (SD) age 54.7 (12) years) had an abnormal diastolic blood pressure response that appeared 1.2 (0.3) min before ST segment deviation and became normal 0.9 (0.3) min after the ST segment returned to normal. Group 2: 40 (80%) patients (12 with one, 16 with two, and 12 with three vessel coronary arteries disease) (aged 56.8 (8.2) years) had a normal diastolic blood pressure response to stress testing. The ejection fraction (46.3 (5)%) and cardiac index (2.6 (0.1) 1/min/m2) in group 1 were less than in group 2 (61.6 (4.2)% and 3.8 (0.3) 1/min/m2 respectively, p < or = 0.001). The end systolic volume was greater in group 1 than in group 2: 38.7 (0.7 ml/m2 v 28.2 (2.1) ml/m2, p < or = 0.001. CONCLUSION--In patients with coronary artery disease an abnormal increase in diastolic blood pressure during exercise stress testing correlated well with left ventricular systolic function at rest but not with the number of obstructed coronary arteries. The abnormal response of diastolic blood pressure probably reflects deterioration of myocardial function.     

Postexercise blood pressure reduction in elderly hypertensive patients

OBJECTIVES: We sought to study: 1) the impact of hemodynamic and left ventricular function on short-term postexercise blood pressure reduction in elderly hypertensive patients; and 2) the 22-h postexercise effects on ambulatory blood pressure in elderly hypertensive patients. BACKGROUND: Although early exercise provokes postexercise blood pressure reduction, the mechanisms underlying this response are not completely understood. Besides, it is unclear whether the reduction in blood pressure after exercise lasts long enough to have clinical relevance in elderly hypertensive patients. METHODS: We studied 24 elderly hypertensive patients (age 68.9 +/- 1.5 years) and 18 age-matched normotensive control subjects (age 68.1 +/- 1.2 years). Cardiac output (carbon dioxide rebreathing) and blood pressure (auscultatory) were measured at rest and after a 45-min period of low-intensity bicycle exercise (50% maximal oxygen uptake) and at 15, 30, 60 and 90 min after exercise. Left ventricular function (by Doppler echocardiography) was also evaluated. Ambulatory blood pressure monitoring was evaluated after 45 min of exercise or 45 min of rest, in a randomized order. RESULTS: In the hypertensive patients, exercise provoked a significant reduction in blood pressure, cardiac output, stroke volume and left ventricular end-diastolic volume. It also provoked a significant reduction in systolic, mean and diastolic blood pressure during a 22-h period, at daytime and nighttime. CONCLUSIONS: The short-term reduction in blood pressure after exercise in elderly hypertensive patients is associated with a decrease in stroke volume and left ventricular end-diastolic volume. The 22-h postexercise reduction in blood pressure demonstrates the clinical relevance of low-intensity exercise in elderly hypertensive patients.     

Effect of cilnidipine on left ventricular function in hypertensive patients as assessed by tissue Doppler Tei index

Tissue Doppler Tei index is pointed to be more effective in the evaluation of global cardiac function than systolic and diastolic measurements alone in various heart diseases. This study was designed to assess the effect of cilnidipine on left ventricular function in hypertensive patients by using this index. A group of 40 hypertensives (mean age 55+/-8 years, range: 35-65) and 16 controls (mean age 52+/-9 years, range: 36-65) were included. Hypertensives were classified into non-left ventricular hypertrophy (NLVH) group (25 patients) and left ventricular hypertrophy (LVH) group (15 patients), and treated with cilnidipine for 2 months. Before and after treatment, the participants were examined by echocardiography. Tissue Doppler Tei index was calculated as diastolic time interval measured from end of late diastole to origin of early diastole (a') minus systolic Sm duration (b') divided by b', that is Tei index = (a'-b')/b'. Thirty-seven hypertensive patients finished the treatment. Tei index was significantly higher in NLVH and LVH groups than in control group, and in LVH group than in NLVH group (0.44+/-0.07 vs 0.28+/-0.06, P < 0.001; 0.51+/-0.13 vs 0.28+/-0.06, P < 0.001; 0.51+/-0.13 vs 0.44+/-0.07, P < 0.05). After treatment, Tei index was significantly decreased (0.40+/-0.11 vs 0.46+/-0.10, P < 0.0001); systolic blood pressure and diastolic blood pressure were also decreased significantly. In conclusion, Tei index is impaired in hypertensives before development of ventricular hypertrophy and impairment is more prominent in hypertrophy. Cilnidipine can improve left ventricular function. Tissue Doppler Tei index is gaining importance in evaluating LV function after drug intervention in hypertensive patients.     

Left ventricular morphology and diastolic function in uraemia: echocardiographic evidence of a specific cardiomyopathy.

OBJECTIVE--To see whether cardiac morphological and functional abnormalities in uraemic patients are determined by high blood pressure or if they are an expression of a specific cardiomyopathy. DESIGN--Cross sectional study. SETTING--City general hospital in Italy. SUBJECTS--35 uraemic patients receiving haemodialysis (17 men, 18 women; mean age 60.3 (11.2); mean duration of dialysis 52 months) were selected from the 64 patients in Venice who were receiving dialysis; subjects with diabetes, haemochromatosis, valvar dysfunction, regional dyskinesias, and pericarditis were excluded. 19 control normotensive subjects (6 men and 13 women), matched for age. MAIN OUTCOME MEASURES--Echocardiographic measurements of left atrium, left ventricular end diastolic and end systolic volume, aortic root diameter, posterior wall and interventricular septum thickness, left ventricle mass index, and ejection fraction in controls and in patients according to whether they were normotensive (five men, eight women) or hypertensive (12 men, 10 women) on 48 hour ambulatory monitoring; left ventricular diastolic function by Doppler ultrasonography. RESULTS--Mean systolic and diastolic pressures, daytime systolic and diastolic pressures, and night time systolic and diastolic pressures were significantly higher in the hypertensive patients than in the normotensive patients. The normotensive patients had similar blood pressures to the controls. Left ventricular mass correlated significantly with the mean diastolic pressure and mean night time systolic and diastolic pressures. Parathyroid hormone concentrations were similar in the two groups of patients. Diastolic relaxation was impaired to the same degree in the two groups of patients. Parameters of diastolic function showed no relation to left ventricular mass, which was significantly higher in the hypertensive than in the normotensive patients. CONCLUSIONS--Uraemia is likely to induce specific changes in the relaxation properties of the myocardium. These changes are responsible for the impaired diastolic function independently of blood pressure, degree of hypertrophy, and metabolic changes, which suggests the existence of a specific cardiomyopathy. Hypertension remains a determinant of left ventricular mass.     

生长激素对心功能作用的探讨

目的探讨生长激素（ＧＨ）对心功能的作用。方法用平衡法核素心血池显象技术及运动试验对特发性生长激素缺乏症（ＩＧＨＤ）患者在ＧＨ治疗前后进行左心室功能评价。结果６７例儿童及青少年两组患者左心室总体射血分数（ＬＶＥＦ）明显低于对照组（分别为Ｐ＜０．０５及Ｐ＜０．０１）,青少年组其左心室舒张末期高峰充盈率（ＰＦＲ）也显著低于对照组（Ｐ＜０．０５）;３５例（５２．２％）左心室总体收缩或（和）舒张功能降低;２９例（４７．３％）运动试验后出现心率、ＳＴ段及Ｔ波异常。１３例心功能异常者接受重组人生长激素（ｒｈＧＨ）治疗６个月后,ＬＶＥＦ及ＰＦＲ较治疗前显著提高（分别为Ｐ＜０．０５及Ｐ＜０．０１）。结论约半数生长激素缺乏症（ＧＨＤ）患者在没有ＧＨ治疗的情况下,其左心室收缩和舒张功能明显受损,并伴有心肌缺血和劳损。ＧＨ治疗可显著改善ＧＨＤ患者的心功能。     

Early detection of myocardial alterations in mitral insufficiency with the angiotensin test

Left ventricular function was assessed at rest and after increasing systemic arterial resistance by angiotensin in 40 patients with isolated mitral insufficiency. Angiotensin was administered intravenously at a dose of 0,4 micrograms/mn until the systolic blood pressure rose by at least 30 mm Hg. Left ventricular and aortic pressures, cardiac index and left ventriculography in the 30 degree right anterior oblique projection (50 frames per second) were recorded before and during angiotensin infusion. The mean rise in systolic left ventricular pressure was 40 +/- 2,8 mm Hg; the heart rate increased slightly but significantly; left ventricular and diastolic pressure rose from 12,0 +/- 1,0 to 24,0 +/- 1,2 mmHg. The systolic index (Fick's method) was significantly decreased (37 +/- 1,6 ml/m2 to 26 +/- 1,6 ml/m2) though the angiographic systolic index remained unchanged. This is explained by an increase in the regurgitant fraction (51 +/- 2,5% ao 65 +/- 3%). The end diastolic volume index was unchanged; the ejection fraction was significantly decreased. The resting hemodynamic status was only slightly disturbed in 29 patients (mean capillary pressure less than 15 mm Hg, 8,8 +/- 0,52 mmHg). The left ventricular function curves with angiotensin distinguished two groups of patients: Group A (20 patients) with left ventricular dysfunction induced by angiotensin, Group B (9 patients) who maintained the systolic index despite the increase in left ventricular end diastolic pressure. These results suggest that the angiotensin test may be useful for detecting early left ventricular dysfunction in patients with isolated mitral insufficiency and virtually normal resting hemodynamic parameters.     

Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency

CONTEXT: GH secretion and response to GH replacement are gender-related. OBJECTIVE: The objective of this study was to investigate the effects of GH deficiency (GHD) and replacement on the cardiovascular system according to gender. DESIGN: The design was open and prospective. SETTING: The study was conducted at a university hospital. SUBJECTS: Subjects included 36 severe adult-onset GHD patients (18 men, 20 women, aged < 45 yr); 36 gender-, age-, and body mass index-matched healthy subjects served as controls. INTERVENTIONS: Subjects received GH replacement at a median dose of 6.5 microg/kg.d in men and 7.7 microg/kg.d in women for 2 yr. MAIN OUTCOME MEASURES: Homeostasis model assessment index, total to HDL cholesterol ratio, fibrinogen and C-reactive protein levels, left ventricular mass index, blood pressure, heart rate, diastolic filling, and systolic function at rest and at peak exercise and intima-media thickness (IMT) at common carotid arteries were measured. RESULTS: Basal prevalence and/or degree of insulin resistance, lipid alterations, compromised cardiac function, and IMT were similar in women and men. Diastolic dysfunction was more prevalent in men (61 vs. 25%, P = 0.036). After GH replacement, IGF-I levels normalized in all patients. Lipid profile, fibrinogen, and C-reactive protein levels normalized in all cases. The total to HDL ratio (P = 0.04) was higher in women than men. The homeostasis model assessment index persisted higher in GHD patients than controls and decreased only in GHD men (P = 0.017). Left ventricular mass index normalized during treatment in both women and men, abnormal diastolic function persisted in three women (P = 0.031), and abnormal systolic performance persisted in six women and one man (P = 0.13). IMT decreased similarly in women and men, persisting higher than in controls. Exercise performance normalized in all. CONCLUSIONS: Two-year GH replacement has similar beneficial effects on cardiac and exercise performance and atherosclerosis in women and men with severe GHD.     

Ambulatory monitoring of blood pressure in growth hormone-deficient adults

The aim of this study was to evaluate the 24-h pattern of blood pressure in adults with growth hormone deficiency using ambulatory blood pressure monitoring. We therefore evaluated the mean systolic and diastolic blood pressures, systolic and diastolic blood pressure loads and diurnal blood pressure rhythm. We used an auscultatory-type monitor, the measurements being made at 10-15 min intervals during the day and 20-30 min intervals at night. We included patients with a growth hormone peak of less than 3 ng/ml in at least two stimulation tests: the insulin tolerance and glucagon tests. The exclusion criteria were mental illnesses, pregnancy, diabetes mellitus, blood pressure higher than 160/90 mmHg, the use of growth hormone in the previous 12 months, severe acute illnesses, chronic liver or kidney disease and a history of malignancy. The results were interpreted according to the II Brazilian Consensus for the utilization of ambulatory monitoring. The study population comprised 27 adult patients with growth hormone deficiency, 11 male and 16 female, with an age range of 21-62 years. Five had developed the condition during childhood, whereas the remainder had adult-onset growth hormone deficiency. The mean systolic (115 +/- 16.7 mmHg) and diastolic blood pressure loads (75.51 +/- 1.90 mmHg) were normal. There was a tendency towards a lower blood pressure in patients with childhood-onset growth hormone deficiency when compared with their adult-onset counterparts. Men had a lower systolic blood pressure than women, the same pattern being found for mean diastolic blood pressure. Multiple regression analysis showed that age was the only independent variable with the statistical power to explain the variance of blood pressure in this group of patients. The incidence of non-dippers was 37.03%. Growth hormone deficiency thus seems to be associated with a change in the 24-h blood pressure pattern, with a high incidence of non-dippers.     

Impaired left ventricular function during exercise in coronary artery disease and exertional hypotension

To characterize the hemodynamic abnormalities responsible for exertional hypotension coronary artery disease, we studied 11 patients with exertional hypotension during supine cycle ergometer exercise, defined as greater than 10 mm Hg decrease in systolic blood pressure during exercise, and 11 patients without exertional hypotension (controls). Patients were similar with respect to age, left ventricular ejection fraction at rest, and the intensity of exercise relative to maximal treadmill exercise capacity. Peak exercise ejection fraction, determined by radionuclide ventriculography, was significantly lower in patients with, than in those without exertional hypotension (50 +/- 3 vs. 56 +/- 3%; p less than 0.025). Ejection fraction and stroke volume decreased with exercise in patients with exertional hypotension but not in the controls even though changes in end-diastolic volume and mean blood pressure were similar in both groups. Peak exercise systolic blood pressure and rate pressure product were significantly lower in the patients with exertional hypotension than those without. The exercise-induced regional left ventricular contraction abnormalities were more prominent, extensive and frequent in patients with exertional hypotension than controls. Impairment of left ventricular contractile function was further evident by an abnormal end-systolic volume-systolic blood pressure relation in patients with exertional hypotension. These patients attained a much smaller increase in systolic blood pressure compared with controls despite no statistically significant differences in end-systolic volume response to exercise. These findings suggest that exertional hypotension in patients with ischemic heart disease is associated with exercise-induced left ventricular systolic dysfunction secondary to extensive myocardial ischemia.     

Cardiac Manifestations of Exhaustive Exercise in Nonathletic Adults: Does Cardiac Fatigue Occur?

The aim of the study was to examine the impact of prolonged exercise leading to physical exhaustion on left ventricular (LV) systolic and diastolic function in untrained healthy subjects, and to examine cardiovascular determinants of exercise performance. Twenty-four nonathletic healthy adults (14 males, 10 females; mean age 42 +/- 11 years) were exercised on a treadmill at 70% of maximal oxygen consumption until physical exhaustion occurred after an average of 84 +/- 39 minutes. Two-dimensional and Doppler echocardiography was performed before and 15 minutes after exercise to assess LV function and geometry, and right ventricular (RV) systolic function. After prolonged exercise, LV ejection fraction and geometry were unchanged, but LV end-diastolic volume, end-systolic volume, and stroke volume decreased. However, due to a higher heart rate (HR), cardiac output increased at 15 minutes post exercise. RV fractional shortening was unchanged. LV peak early to atrial filling velocity ratio decreased post exercise, with an increase in percent atrial contribution. However, less preload-dependent variables of LV diastolic function such as deceleration time, LV inflow propagation rate, mitral annular tissue Doppler and myocardial performance index were unchanged. Preexercise stroke volume and HR were the only predictors (r = 0.86, P < 0.01) of exercise duration. However, age, resting blood pressure, indices of systolic and diastolic function, and LV geometry were not predictors. Prolonged exercise leading to physical exhaustion is not associated with systolic or diastolic dysfunction. Reduced early LV diastolic filling and the relative increase in left atrial contribution seen with prolonged exercise are likely due to preload reduction rather than true diastolic dysfunction.     

Exercise systolic blood pressure: a powerful determinant of increased left ventricular mass in patients with hypertension

This study examines the relation between left ventricular mass determined by two-dimensional echocardiography and exercise blood pressure in patients with hypertension. Sixty-seven patients with hypertension and 19 normal subjects underwent treadmill exercise testing and two-dimensional echocardiography. The left ventricular mass index in the normal subjects was 80 +/- 10 g/m2 (mean +/- SD). Patients with hypertension were classified into two groups according to left ventricular mass: Group I (n = 42) had normal mass and Group II (n = 25) had increased mass (greater than 2 SD above the mean value in 19 normal subjects). There was a poor correlation between left ventricular mass and blood pressure at rest. However, a better correlation was found between left ventricular mass and exercise systolic blood pressure (r = 0.58, p less than 0.001) or the change in systolic blood pressure from rest to exercise (r = 0.48, p less than 0.001). Twenty-two (76%) of 29 patients with an exercise systolic blood pressure of 190 mm Hg or greater had an increased left ventricular mass index, whereas only 3 (8%) of 38 patients with an exercise systolic blood pressure of less than 190 mm Hg had an increased left ventricular mass index (p less than 0.0001). Thus, in patients with hypertension, left ventricular mass index is poorly related to blood pressure at rest, but is related to exercise systolic blood pressure. Patients with an exercise systolic blood pressure of 190 mm Hg or greater usually have an increased left ventricular mass. These findings may have therapeutic implications.