The impact of growth hormone/insulin-like growth factor-I axis and nocturnal breathing disorders on cardiovascular features of adult patients with Prader-Willi syndrome

CONTEXT: Adult patients with Prader-Willi syndrome (PWS) are prone to develop obesity, GH deficiency (GHD), and their related complications, with cardiopulmonary failure explaining more than half of PWS fatalities. OBJECTIVE AND STUDY PARTICIPANTS: This study was undertaken to examine the effect of GHD and sleep breathing disorders on cardiovascular risk factors and heart features of 13 PWS (age 26.9 +/- 1.2 yr) and 13 age-, gender-, and body mass index-matched obese individuals (age 26.2 +/- 0.8 yr). RESULTS: Compared with controls, PWS patients had lower GH response to arginine+GHRH, IGF-I levels, triglycerides, total and LDL-cholesterol, insulin, and insulin resistance measured by a homeostatic model approach. Dual-energy x-ray absorptiometry, abdominal computed tomography scans, and polysomnography revealed a greater fat mass, similar abdominal fat, but greater sleep breathing disorders in PWS than obese subjects. Echocardiography showed no systolic or diastolic alteration, although PWS had lower left ventricle (LV) mass (135.7 +/- 7.7 vs. 163.5 +/- 8.4 g, P < 0.05) and near significantly lower values of LV end-diastole diameter (P = 0.08), compared with obese controls. Baseline radionuclide angiography documented comparable values of systolic and diastolic values between groups. However, adrenergic stimulation with dobutamine caused a lower increase of LV ejection fraction (71.9 +/- 1.9 vs. 76.3 +/- 1.2%, P < 0.05) and heart rate (103 +/- 6.9 vs. 128 +/- 2.8 beats/min, P < 0.05) in PWS than obese individuals. By multivariate analysis, nocturnal oxygen desaturation and IGF-I levels were main significant predictors of LV mass and heart rate in PWS patients. CONCLUSIONS: PWS differs from simple obesity by a healthier metabolic profile, impaired nocturnal breathing, decreased heart geometry, and systolic and chronotropic performance. GHD and the predictive role of IGF-I on structural and functional heart parameters suggest a GH/IGF-I-mediated control of cardiac risk in PWS.     

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。     

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.     

心肌梗死并心功能不全患者冠状动脉介入治疗的作用

目的 :评价心肌梗死 (MI)并左心功能不全患者经皮冠状动脉介入术 (PCI)对左心收缩功能和左心室重构的作用。方法 :5 2例MI并左心功能不全患者 ,急性心肌梗死 (AMI) 30例 ,陈旧性心肌梗死 (OMI) 2 2例 ,行经皮腔内冠状动脉成形术加支架术治疗 ,术后随访 3个月 ,超声心动图测定左室舒张末内径 (LVEd)、左心房内径(LAd)、左室舒张末容积 (LVEDV)、左室收缩末容积 (LVESV)、左室射血分数 (LVEF)和左室短轴缩短率 (LVFS) ,比较治疗前后各参数的变化。结果 :PCI治疗后LVEd、LAd、LVEDV、LVESV较治疗前均明显减少 (均P <0 .0 1)、LVEF和LVFS明显增高 (P <0 .0 1) ,尤以AMI组明显 ,并且冠状动脉血运重建的时间越早 ,心功能恢复越好。结论 :MI并左心功能不全患者尽早PCI治疗可明显改善左心室收缩功能 ,部分阻抑左心室重构。     

Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance

AIM: The aim of the current study was to evaluate the effect of short-term (6 months) and long-term (18 months) treatment with pegvisomant on cardiac structure and performance in patients with acromegaly. PATIENTS: Seventeen patients (nine women, eight men, 27-61 yr) with active acromegaly entered and 12 completed the long-term study. After a baseline evaluation, including measurement of hemodynamic, biochemical, and hormonal parameters, and a standard Doppler echocardiography, treatment with pegvisomant was started at the initial dose of 10 mg/d, increasing by 5 mg/d every 6 wk on the basis of IGF-I levels until normalization or the achievement of a maximal dose of 40 mg/d. RESULTS: After short-term treatment, IGF-I levels were normalized in 10 of the 17 (59%) patients. Left ventricular mass index (LVMi) was significantly decreased without changes in diastolic and systolic performance. After long-term treatment, IGF-I levels were normalized in 10 of the 12 (83%) patients. Blood glucose and serum insulin levels were decreased compared with baseline. LVMi was further decreased compared with short-term treatment, so that the prevalence of left ventricle hypertrophy decreased from 50% at baseline to 17% after 18 months of treatment. Moreover, ejection fraction as well as early to late (atrial) peak velocity ratio (E/A) were significantly increased, whereas isovolumic relaxation time was significantly decreased compared with baseline, demonstrating an improvement of both diastolic and systolic function. A significant correlation was found between the change in IGF-I levels and that of left ventricular ejection fraction. In general, the prevalence of cardiac insufficiency was present in 13 of the 17 (76%) patients at baseline and in one (8%) patient after 18 months of treatment. CONCLUSIONS: Long-term treatment with the GH receptor antagonist improves acromegalic cardiomyopathy by decreasing cardiac hypertrophy and enhancing diastolic and systolic function, and consequently partially or completely reverting the cardiac insufficiency.     

Six months of recombinant human GH therapy in patients with ischemic cardiac failure does not influence left ventricular function and mass

Beneficial effects of recombinant human GH on cardiac function have been reported in humans with GH deficiency and in patients with idiopathic dilated cardiomyopathy. No randomized controlled trial has been performed on the effects of recombinant human GH on cardiac function in patients with ischemic cardiac failure. We therefore randomly assigned 22 patients with ischemic cardiac failure (left ventricular ejection fraction, <40%; 19 men and 3 women; mean age, 64 yr) to receive 6 months of unblinded therapy with recombinant human GH (2.0 IU/d) or no treatment. Primary end points were left ventricular ejection fraction and left ventricular mass. Left ventricular end-diastolic volume, left ventricular end-systolic volume, and myocardial perfusion, both at rest and during exercise, were assessed as well. Cardiac imaging techniques were electrocardiographically gated single photon emission computer tomography and magnetic resonance imaging. In addition, biochemical and biometric measurements were performed. Nineteen patients completed the study (10 controls and 9 GH-treated subjects). IGF-I and IGF-binding protein-3 increased significantly after recombinant human GH treatment (+24% and +58%, respectively) compared with control values (-14% and +5%; P < 0.05). Left ventricular ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular mass, and myocardial perfusion were not influenced by recombinant human GH therapy. We conclude that 6 months of recombinant human GH treatment in patients with ischemic cardiac failure had no beneficial effect on left ventricular function and mass.     

Subtle Cardiovascular Abnormalities in Prader-Willi Syndrome Might Begin in Young Adulthood

Objective Patients with Prader-Willi syndrome (PWS) are known to have a high mortality rate. However, little is known about the exact reason for this, particularly in adults, because so few reports have been published. The present study examined cardiovascular abnormalities to determine the cause of death in adults with PWS. Methods From September 2017 to April 2019, a total of 18 adults with PWS, and, no history of cardiovascular diseases, were enrolled. We investigated the levels of the cardiovascular biomarkers: high-sensitivity C-reactive protein (hs-CRP) and troponin T (TnT). To estimate the cardiac function, we measured the left ventricular ejection fraction (LVEF), global longitudinal systolic strain (GLS) of the left ventricle, ratio of peak early mitral filling velocity (E) to early diastolic mitral annular velocity (E/e'' ratio), mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) using standard and tissue Doppler echocardiography. Results The mean patient age was 28±9 years old. There were 11 men, and the mean body mass index was 45.1 kg/m². Dyslipidemia (82%), diabetes mellitus (82%) and hypertension (83%) were commonly found as comorbidities. Most patients had elevated levels of hs-CRP (mean 1.007±0.538 mg/dL). The LVEF (mean 61%±5%) showed normal values, while the GLS (mean 15.0%±3.0%) was decreased. The TAPSE was mildly reduced (mean 16±3 mm). Conclusion These results suggest that subtle cardiovascular abnormalities have already begun in young adults with PWS. We need to manage obesity and the resultant obesity-related disorders in order to prevent heart failure and coronary atherosclerosis in PWS patients.     

Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults

GH deficiency (GHD) in adulthood is accompanied by physical and psychological impairments. One hundred fifteen patients (67 male, 48 female) with pronounced GHD were enrolled in a randomized, double-blind, placebo-controlled study with objectives that included effects on body composition, cardiac structure, and function and safety of replacement therapy with recombinant human GH (Saizen). Sixty patients (31 male, 29 female) received GH at a dose of 0.005-0.010 mg/kg.d, and 55 patients (36 male, 19 female) received placebo for 6 months. Assessment of body composition by dual-energy x-ray absorptiometry demonstrated a treatment difference in lean body mass increase of 2.1 kg (between-group comparison, P < 0.0001), which was significantly greater among males than females (P < 0.0001) [males: GH, +3.13 kg (2.42, 3.84); placebo, +0.11 kg (-0.60, 0.82); and females: GH, +0.64 kg (-0.15, 1.44); placebo: -0.90 kg (-2.20, 0.39)] [mean change 0-6 months (95% confidence limits)] and was associated with IGF-I changes. The decrease in fat mass of 2.8 kg (between-group comparison, P < 0.0001) noted by DEXA was also evident from bioelectric impedance and anthropometric measurements. Echocardiography showed comparable improvement in left ventricular systolic function after GH treatment in both genders. End-systolic volume decreased by 4.3 +/- 10.5 ml (from 35.8 +/- 17.6 ml; between-group comparison, P = 0.035) and ejection fraction increased by 5.1 +/- 10.0% (from 55.0 +/- 11.2%; between-group comparison, P = 0.048), approaching normalcy. Diastolic function did not change as assessed by isovolumic relaxation time, early diastolic flow, diastolic flow secondary to atrial contraction, or ratio of peak mitral early diastolic and atrial contraction velocity. GH treatment was well tolerated, with adverse events primarily related to effects on fluid balance. No apparent relationship between IGF-I levels and the occurrence or severity of adverse events was identified. In conclusion, GH replacement therapy in adults with GHD demonstrated beneficial effects on lean body mass composition that was more pronounced in males than females. In contrast, cardiac function improvement appears to benefit both genders equally.     

Circulating IGF-I levels in monitoring and predicting efficacy during long-term GH treatment of GH-deficient adults

OBJECTIVE: To investigate the effects of long-term GH in GH-deficient adults, as predicted by IGF-I levels. METHODS: Patients received GH, 5 microg/kg per day for 1 Month and 10 microg/kg per day for another 12-30 Months. Changes in body composition, cardiac structure/function, serum lipids and quality of life were measured. RESULTS: There was a significant increase in lean body mass (LBM) (2.21 kg; P<0.0001) after 6 Months, which was sustained throughout treatment. A larger increase occurred in males than females (2.97 vs 1.19 kg; P<0.0001). Total fat mass was reduced (2.56 kg; P<0.0001 (3.26 kg males, 1.63 kg females)). Responsiveness to GH varied greatly, but LBM changes correlated with IGF-I changes (P<0.004). Furthermore, thinner patients experienced greater and progressive LBM increases. There was an increase in ejection fraction (3.85+/-9.95%; P=0.0002) after 6 Months, sustained to 18 Months. These cardiac effects were equal for males and females, and did not correlate with IGF-I levels. Serum low-density lipoprotein/high-density lipoprotein ratios decreased within 6 Months, and were sustained thereafter. Quality of life improved significantly after 6 Months, an effect that was sustained/enhanced as treatment continued. No major adverse events were identified. CONCLUSIONS: Improved body composition is both reflected by IGF-I changes and predicted inversely by baseline adiposity. Other effects of GH replacement on cardiac function, dyslipidaemia and quality of life, however, do not correlate with circulating IGF-I concentrations. Our findings validate the importance of sustained GH therapy, but caution on the interpretation of IGF-I levels in monitoring the long-term effects of GH treatment.     

Growth hormone treatment improves body composition in adults with Prader-Willi syndrome

OBJECTIVE: Low growth hormone (GH) secretion and hypogonadism are common in patients with Prader-Willi syndrome (PWS). In this study we present the effects of GH treatment on body composition and metabolism in adults with PWS. PATIENTS AND MEASUREMENTS: Nineteen patients with clinical PWS were recruited, 13 had PWS genotype. They were randomised to treatment with placebo or GH (Genotropin, Pharmacia Corporation, Sweden) 0.8 IU (0.2 mg) daily for 1 month and then 1.6 IU (0.5 mg) daily for 5 months. Thereafter patients received open label treatment so that all had 12 months of active GH treatment. Doses were individually titrated to keep serum IGF-I within the normal range for age. Body composition using dual energy X-ray absorptiometry (DXA), metabolic and endocrinological parameters, including oral glucose tolerance test (OGTT), were studied every 6 months. Seventeen patients, nine men and eight women, 17-32 years of age, with a mean body mass index (BMI) of 35 +/- 3.2 kg/m2 completed the study. RESULTS: Compared to placebo, GH treatment increased IGF-I (P < 0.01) levels and decreased body fat (P = 0.04). When all patients recieved GH treatment a mean reduction in body fat of 2.5% (P < 0.01) concomitant with a mean increase in lean body mass of 2.2 kg (P < 0.05) was seen. Significant changes in body composition were only seen in the patients with the PWS genotype. Lipid profiles were normal in most patients before treatment and did not change. OGTT was impaired in five patients at 12 months, but two of these patients increased in fat mass. Insulin levels were unchanged. According to homeostasis model assessment (HOMA), insulin resistance did not change. Side-effects attributed to water retention occurred in three patients, one of whom had to be given increased diuretic therapy. CONCLUSION: This study shows beneficial effects of GH treatment on body composition in adult PWS patients without significant side-effects. Consequently, further studies are encouraged.     

替米沙坦治疗充血性心力衰竭的临床观察

目的 :观察替米沙坦治疗慢性充血性心力衰竭 （CHF）的临床疗效。方法 :经强心、利尿、扩血管等治疗 ,疗效不佳的 CHF患者 96例口服替米沙坦 4 0～ 80 mg,每天 1次 ,疗程 4周。观察治疗前后血压、心率、左室舒张末内径、左室射血分数以及心功能变化。结果 :4周治疗后血压、心率、左室舒张末内径均明显下降 （P<0 .0 5 ）。左室射血分数、心排出量、心脏排血指数等各项指标均明显增加 （P<0 .0 1） ,心功能改善 ,临床总有效率达 98% ,患者耐受性好。结论 ::替米沙坦治疗 CHF疗效好。     

Tei指数及脑钠肽评估先天性心脏病婴儿术前左心功能的研究

目的探讨检测血清脑钠肽浓度结合左心室Tei指数评估先天性心脏病婴儿术前左心功能的临床应用价值。方法选择先天性心脏病患儿60例为试验组,同期小儿外科住院患儿20例为对照组,将心功能分为四级,用多普勒超声心动图测量左心室Tei指数及左心室射血分数,采用酶联免疫吸附法(ELISA)检测血清BNP浓度。结果患儿血清BNP浓度、左心室Tei指数在心功能0级、Ⅰ级、Ⅱ级、Ⅲ级组呈逐渐增高趋势,左心室射血分数呈逐渐减低趋势,且方差分析显示各组间均数比较,差异有统计学意义(P0.01)。直线相关分析显示,血清BNP浓度与左心室Tei指数、心功能分级具有良好的正相关关系(r1=0.73,P0.01;r2=0.62,P0.01),与左心室射血分数具有负相关关系(r3=-0.48,P0.01);左心室Tei指数与心功能分级呈正相关关系(r4=0.57,P0.01),与左心室射血分数呈负相关关系(r5=-0.52,P0.01);左心室射血分数与心功能分级呈负相关关系(r=-0.56,P0.01)。结论 Tei指数及血清BNP浓度能够迅速、准确评估术前先天性心脏病婴儿心功能,具有临床推广应用价值。     

Echocardiographic dimensions and function in adults with primary growth hormone resistance (Laron syndrome)

Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress.     

Synergistic effect of captopril and dobutamine on left ventricular pressure—volume and pressure—shortening relations in severe cardiac failure

The acute effects of captopril and dobutamine, alone and in combination, on left ventricular contractility were assessed from left ventricular end-systolic pressure—volume and pressure—shortening relations in 6 patients with severe end-stage cardiac failure. Dobutamine was given by constant intravenous infusion on two occasions 48 hours apart, on one of these occasions the patient also received oral captopril in a dose of 37±12 mg 6-hourly. Pressures and cardiac index were measured, and left ventricular volumes and ejection fraction computed from simulta-neously recorded radionuclide ventriculography. Dobutamine alone did not cause a statistically significant increase in stroke index, stroke work index, cardiac index and ejection fraction, although pulmonary capillary wedge pressure and right atrial pressure fell (P < 0.05). These was no change in systemic or pulmonary vascular resistance nor in arterial blood pressure. Following administration of captopril, diastolic arterial pressure decreased (P < 0.05), and the dobutamine challenge produced a greater and significant rise in stroke and stroke work index (P < 0.05) and cardiac index (P < 0.01). The left ventricular contractile state was unaltered by captopril but appeared to increase with dobutamine and more so during combined therapy with captopril and dobutamine, indicating a synergistic effect of the two drugs when given in combination.     

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 heart: an end-organ of GH action

Several experimental and clinical studies have indicate that the heart is an end-organ of GH action. Patients with either childhood- or adulthood-onset GH deficiency (GHD) have abnormalities of cardiac structure and function, such as reduced cardiac mass, impaired diastolic filling and reduced left ventricular response at peak exercise. These cardiovascular abnormalities can be reversed, at least partially, after GH replacement therapy. On the other hand, the chronic overproduction of GH and IGF-I in acromegaly leads to the development of a specific cardiomyopathy. Concentric cardiac hypertrophy occurs in more than two-thirds of patients at diagnosis and is commonly associated with diastolic dysfunction. In later stages, impaired systolic function ending in heart failure can occur if GH/IGF-I excess is not controlled. Additionally, acromegalic cardiomyopathy is complicated by abnormalities of cardiac rhythm and cardiac valves. Successful control of acromegaly is accompanied by a decrease of the left ventricular mass and improvement of cardiac function. These beneficial effects appear earlier in young patients with short disease duration than in elderly patients. In conclusion, GH and IGF-I play a main role in the regulation of cardiac development and performance.     

经皮冠状动脉介入治疗对心肌梗死患者心功能的影响

目的 :评价心肌梗死并左心功能不全患者经皮冠状动脉介入 （PCI）治疗对左心收缩功能和左心室重构的影响。方法 :急性心肌梗死 （AMI）患者 30例 ,陈旧性心肌梗死 （OMI） 2 2例 ,经 PTCA、支架术治疗 ,术后随访 3个月 ,超声心动图测定左室舒张末内径 （L VEd）、左心房内径 （L Ad）、左室舒张末容积 （L VEDV）、左室收缩末容积（L VESV）、左室射血分数 （L VEF）和左室短轴缩短率 （L VFS） ,比较治疗前后各参数的变化。结果 :PCI治疗后L VEd、L Ad、L VEDV、L VESV显著减少 （P<0 .0 1）、L VEF和 L VFS显著增高 （P<0 .0 1） ,尤以 AMI组明显 ,并且冠状动脉血运重建的时间越早 ,心功能恢复越好。结论 :心肌梗死并左心功能不全患者尽早 PCI治疗可明显改善左心室收缩功能 ,可部份阻抑左心室重构。     

Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency

Adult GH deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to unfavorable lipid profile, hyperfibrinogenemia, and impairment of cardiac performance. This prospective controlled cohort study evaluated the effects of 12-month GH replacement on lipid profile, fibrinogen levels, cardiac mass by echocardiography, and performance by equilibrium radionuclide angiography. To this end we studied 20 patients (11 men and 9 women, aged 19-40 yr), 10 with childhood-onset (co-) and 10 with adult-onset (ao-) disease, and 20 sex- and age-matched healthy subjects. At study entry, insulin-like growth factor I (IGF-I; P < 0.0001) and high density lipoprotein (HDL) cholesterol (P < 0.0001) levels, left ventricular mass index (LVMi; P < 0.0001), ejection fraction (LVEF) at rest (P = 0.001) and at peak exercise (P < 0.0001), peak ejection rate (P = 0.005), and exercise duration (P < 0.0001) and capacity (P = 0.002) were lower, whereas total cholesterol (P = 0.02), triglycerides (P = 0.003), and fibrinogen (P = 0.005) levels were higher in patients than in controls. After 12 months, increases in IGF-I (P < 0.0001) and HDL cholesterol levels (P = 0.04), LVMi (P < 0.0001), LVEF at peak exercise (P < 0.0001), and exercise duration (P = 0.009) and capacity (P = 0.003) and decreases in total cholesterol (P < 0.0001), low density lipoprotein cholesterol (P < 0.0001), triglycerides (P < 0.0001), and fibrinogen (P = 0.01) levels were found in all patients, without any difference between co- and ao-GHD. At the end of treatment, however, total cholesterol, triglycerides, and fibrinogen levels were still higher, and HDL cholesterol levels, IGF-I levels, and LVEF at rest and at peak exercise were lower in patients than in controls. In conclusion, GH replacement for 12 months significantly improved lipid profile, decreased fibrinogen levels, and increased LVMi and LVEF in young adults with co- or ao-GHD. However, lipid profile, fibrinogen levels, and systolic function remained abnormal compared with those in age- and sex-matched controls, suggesting that a longer period of GH replacement is necessary to normalize cardiovascular parameters and reverse the cardiovascular risk of these patients.     

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.     

心脏再同步化治疗慢性心力衰竭的疗效观察

目的观察心脏再同步化治疗(CRT)慢性心力衰竭(CHF)的临床疗效。方法26例CHF患者行CRT,全部患者均经冠状静脉窦置入左室导线1根至心脏静脉,术后随访13.8±10.4个月,观察心功能,患者活动度及夜间心率、QRS波时限,左室射血分数(LVEF)及相关心功能超声指标。结果24例治疗后心功能改善,2例猝死,有效率92.3%,心功能NYHA分级,从Ⅲ～Ⅳ级改善为Ⅱ～Ⅲ级,患者活动度从0.17±0.24小时/天增加至2.98±0.46小时/天,夜间心率由80.8±12.0次/分降低至61.3±2.5次/分,QRS波时限从158.60±31.86ms缩短至130.95±23.44ms,P<0.05。LVEF从0.21±0.05提高至0.35±0.05,P<0.05,其他相关超声指标较CRT之前明显改善(P均<0.05)。结论CRT是治疗CHF的有效方法。