Early cardiac morphologic and functional changes in neurofibromatosis type 1 hypertensives: an echocardiographic and tissue Doppler study

BACKGROUND: Hypertension is frequently associated with neurofibromatosis type 1 (NF1), a common inherited disease that limits life expectancy. No data are available on cardiac damage in NF1 patients with hypertension. We evaluated cardiac function in NF1 patients with hypertension diagnosed by 24-h ambulatory blood pressure monitoring (ABPM), compared with normal children. METHODS: We studied 73 NF1 patients (41 boys; mean age 12 years) and 30 normal children comparable for age and sex, using standard 2D echocardiography, standard Doppler and Doppler tissue imaging (DTI). Twelve patients (16%) showed 24-h systolic blood pressure (SBP) or 24-h diastolic blood pressure (DBP) >95th percentile for age and sex. We divided the NF1 group into two subgroups: group A, patients with 24-h SBP and DBP 95th percentile for age and sex. RESULTS: Group B presented a thicker end-diastolic interventricular septum (p<0.0001), posterior wall (p=0.02), LVMI (p<0.001) and relative wall thickness (p<0.03) than group A and controls. Left atrial dimension in group B was also significantly larger. Examination by standard Doppler showed a deceleration and isovolumic relaxation time significantly prolonged in group B. DTI parameters were significantly higher in NF1 patients than controls. In group B, myocardial early diastolic (E(m)) and systolic (S(m)) velocities were significantly lower than group A. Myocardial early/late diastolic ratio (E(m)/A(m)) in NF1 patients was lower than controls and 19% of group A and 20% of group B showed an E(m)/A(m) ratio <1. No healthy subjects presented an E(m)/A(m) ratio <1. CONCLUSIONS: We demonstrated early cardiac morphologic and functional changes in young NF1 patients with hypertension. Because DTI directly studies cardiac muscle, it can detect changes induced by hypertension as well as those independent of blood pressure.     

Hemarthrosis: an unusual complication of type 1 neurofibromatosis

Type 1 neurofibromatosis is one of the most common autosomal-dominant disorders and often includes orthopedic manifestations. We report the case of a 48-year-old woman with hemarthrosis caused by a popliteal cyst infiltrated by a diffuse neurofibroma associated with angiodysplasia. Surgical resection of this tumor was followed by postoperative hemorrhagic complications.     

Pattern of heart failure in Abuja,Nigeria: an echocardiographic study

Aim

Despite heart failure having been identified in subjects in sub-Saharan Africa over the last 60 years, there is still a dearth of data, especially echocardiographic data on heart failure. We therefore set out to analyse the clinical and echocardiographic features of all consecutive subjects presenting with heart failure in a tertiary institution in Nigeria.

Methods

Three hundred and forty subjects with heart failure, according to the guidelines of the European Society of Cardiology, were studied. Each patient had two-dimensional guided transthoracic echocardiography.

Results

The mean age of the patients was 50.60 ± 15.29 years, and 50.9% of the study population were males while 49.1% were females. The commonest cause of heart failure identified was hypertension in 61.5% of the patients; 75.5% had systolic heart failure, whereas 23.5% had heart failure with preserved ejection fraction.

Conclusions

Untreated hypertension has been identified as the leading cause of heart failure in Abuja, Nigeria, which is similar to that in many other parts of sub-Saharan Africa. Coronary artery disease is a rare cause of heart failure in this population group.     

Congenital heart disease in a population of dizygotic twins: an echocardiographic study

BACKGROUND: Congenital heart disease (CHD) is the most common malformation in the fetal and neonatal period but little is known about its cause. The distribution analysis of CHD in dizygotic twins could provide a useful tool to evaluate the role of genetic and environmental factors in the development of CHD. Dizygotic twins are siblings with different genes, growing together in the same womb. AIM OF STUDY: To investigate the occurrence of CHD in a large sample of dizygotic twins of nonconsanguineous healthy parents, comparing the data from non-twin patients. METHODS: From January 1999 to December 2002, we enrolled 1743 CHD patients with, at least 1 sibling, and 66 pairs of dizygotic twins, referred to our tertiary center. The diagnosis of CHD was based on clinical and echocardiographic evaluation. RESULTS: Considering only the sibling nearest in age for each non-twin patient the recurrence was 67/1743 (3.8%). Among these 67 patients, 35 (52.2%) had a sibling with the same or similar CHD. Conversely, considering all 1886 siblings, recurrence of CHD in the non-twin group was 70/1743 (4%). Of the 70 patients, 36 (36/70, 51.4%) had a sibling with the same suspected pathogenic mechanism of CHD. In 9/66 pairs of twins (13.6%), both siblings had a CHD. In the nine pairs of twins in whom both siblings had a CHD, the percentage of concordance (based on the suspected pathogenic mechanism) for CHD was 100% (p<0.05). CONCLUSIONS: Our findings suggest that the higher recurrence and concordance of CHD found in dizygotic twins could depend on some poorly identified environmental risk during the pregnancy.     

1型神经纤维瘤病发病机制的研究进展

1型神经纤维瘤(NF1)是常见的神经系统遗传病,NF1基因突变导致神经纤维蛋白失活或表达下调从而产生以神经纤维瘤为主要特征的一系列神经皮肤损害及合并各种良性和恶性肿瘤。NF1为肿瘤抑制基因,是RAS的负向调节器。NF1相关的肿瘤或NF1缺陷小鼠细胞中神经纤维蛋白的不表达与RAS的活性增加和细胞增殖的增多有关。除神经纤维蛋白介导的RAS活性和神经纤维瘤及相关肿瘤发生之间具有直接的病理生理联系外,其它基因协同的遗传学变化能加速肿瘤的发生,同时修饰基因也能影响对肿瘤的易感性。     

Targeting neovascular pericytes in neurofibromatosis type 1

Apart from tumor-driven neovascularization, a less-appreciated consequence of neurofibromatosis type 1 (NF1) is the hyperproliferation of vascular mural cells (pericytes). This study aims at establishing a role for pericytes in NF1, and determining whether interference with the function of a key pericyte component (NG2 proteoglycan) inhibits NF1 tumor neovascularization. Neovascularization in NF1 was studied in Nf+/+(control), Nf1+/–, and Nf1–/–embryos at E-10, ischemia-induced retinal angiogenesis model in 24 eyes of Nf1+/–, Nf1+/+mice, and in malignant peripheral nerve sheath tumors (MPNSTs) derived from NF1 patients (ST88-14, NMS-2PC) orthotopically grown in nude mice (Crl: nu/nu). The anti-angiogenic effect of intracorneal polymer pellets containing anti-NG2 neutralizing antibody was quantified in the nude-mouse corneal angiogenesis model in which angiogenesis was induced by xenografting NMS-2PC tumor into the corneal stroma of 22 eyes. By using confocal microscopy, immunohistochemistry, and BrdU proliferation assay, the pericyte/endothelium ratios and proliferation rates were measured. Activated pericytes were present at the leading tip of the angiogenic sprouts. Pericytes showed continuous investment of endothelium in both NMS-2PC and ST88-14 MPNST tumor xenografts. Mean corneal angiogenesis induced by NMS-2PC tumor grafts in NG2-antibody treated eyes was 1.491 and 3.186 mm ² in isotype-matched non-immunoglobulin treated eyes (control) (P=0.0002). A total of 193.8 vascular nuclei (a measure of ischemia-induced retinal angiogenesis) was present in angiogenic retinal tufts in Nf1+/– mice compared to 89.23 in Nf1+/+ mice (control) (P < 0.0001). Mean pericyte/endothelium investment ratios were 1.015, 1.380, and 2.084 in control, Nf1+/–, and Nf1–/–embryos, respectively. Pericytes were 23% (control), 49% (Nf1+/–), and 69% (Nf1–/–) BrdU-positive. Endothelial cells from the same embryos were 29% (control), 47% (Nf1+/–), and 62% (Nf1–/–) BrdU-positive. Angiogenesis is accelerated in NF1 due to hyperproliferation of pericytes and endothelial cells. Mitotically activated NG2-positive pericytes, and endothelial cells may serve as potential therapeutic targets in NF1.     

The nature of cardiac hypertrophy in acromegaly: an echocardiographic study

M-mode echocardiography was used to study cardiac involvement in 78 patients with acromegaly. Proportionate concentric or eccentric left ventricular hypertrophy (LVH) was a common finding. Calculated left ventricular mass (LVM) was increased significantly in a hormonally active disease group compared to an inactive disease group or a control group (153 +/- 7 vs. 96 +/- 8 and 89 +/- 3 g/m2 resp.; p less than 0.001 for both). The increase of LVM in hormonally active disease is due to predominantly LV dilatation, whereas associated hypertension, if present, aggravates the LVH exclusively due to thickening of the LV wall. Hypocorticalism, if present, does not influence the degree of LVH. Asymmetric septal hypertrophy was not found to be specific for acromegaly and was seen in only 7.7% of patients. There was no correlation between LVM and both the plasma levels of growth hormone and duration of disease. On the basis of a retrospective analysis of LVM in successfully treated patients the authors conclude that specific heart muscle disease in acromegaly, manifesting itself as LVH, is slowly reversible after cessation of the growth hormone hyperproduction.     

Increased myocardial contractility in short-term Type 1 diabetic patients: an echocardiographic study

Summary Cardiac function was investigated by echocardiography in 24 short-term Type 1 diabetic patients with a mean diabetes duration of 7 years (range 4–14 years) during conditions of ordinary metabolic control. Compared to 24 age and sex matched normal control subjects, measurements of myocardial contractility as left ventricular fractional shortening and mean circumferential shortening velocity were increased by 12% and 20% respectively. Another 8 Type 1 diabetic patients were examined during conditions of poor (hyperglycaemia and ketosis) and good metabolic control. Following improved glycaemic control, left ventricular fractional shortening and mean circumferential shortening velocity decreased by 16% and 24% respectively. Our findings show that short-term Type 1 diabetes is associated with increased myocardial contractility. Furthermore, this condition is related to the state of metabolic control.     

Right atrial myxoma: an echocardiographic study

A case of right atrial myxoma is reported in a 29-year-old man. Though it was a large tumour, the diagnosis remained unsuspected for a long time. Multiple echo recordings strongly contributed to the diagnosis. After surgical removal, the post-operative course was uneventful.     

Isometric exercise in the denervated heart: a Doppler echocardiographic study

The haemodynamic responses to isometric exercise of eight recipients of orthotopic heart transplants and eight healthy controls were studied. Each performed sustained exercise at 30% of maximal voluntary contraction for three minutes on a handgrip dynamometer. Cardiac output was measured by combined Doppler and cross sectional echocardiography before exercise and every 30 seconds during and after exercise. In the controls cardiac output and blood pressure increased significantly owing to an increase in heart rate with no change in stroke volume. In the transplant group cardiac output, heart rate, and stroke volume remained unchanged throughout exercise. In contrast with its response to dynamic exercise the denervated human heart is unable to increase cardiac output during isometric exercise. The pressor response that occurs is mediated via an increase in peripheral vascular resistance.