Working towards risk stratification for ascending aortic dilatation in pediatric Turner syndrome patients: results of a longitudinal echocardiographical observation.

This study aimed to longitudinally evaluate aortic root dimensions and elasticity in pediatric Turner syndrome (TS) in relation to known cardiac implications such as coarctation of the aorta (CoA) and bicuspid aortic valves (BAV) in order to create an improved risk profile for the presumed underlying vessel pathology in childhood. We report on the longitudinal findings of our pediatric TS outpatient clinic over a period of up to 7.6 years. Forty-nine TS patients (median age at baseline 9.7 ± 5.9 years, range 0-19.8) were followed-up for on average 2.9 ± 1.1 examinations and a median time of 3.4 ± 1.6 years. Aortic root (AoR) diameters and corresponding Z-scores were determined echocardiographically, and elasticity parameters as well as annual progression rates were calculated. At baseline, 16.3% of patients showed Z-scores > 2 at one or more levels of the AoR (35.7% of patients with BAV, odds ratio of 4.2). There was net progression to be noted at all measuring levels, leading to 28.6% of patients (50% of patients with BAV) exhibiting aortic dilatation at the end of follow-up. Progression correlated with the presence of BAV, non-mosaic monosomy, and age. A levelling-off of progression was seen with the onset of adolescence. CONCLUSIONS: Marked progression of aortic diameters leading to the development of dilatation can be observed in TS patients during childhood and stresses the importance of close surveillance during childhood. Main risk factors are BAV and complete monosomy 45X0. A beneficial influence of estrogen substitution can be suspected but needs further investigation. WHAT IS KNOWN: • Patients with Turner syndrome are at an increased risk for aortic dilatation and dissection. • The presence of BAV and complete monosomy 45X are additional risk factors. WHAT IS NEW: • Aortic dilatation can be detected in pediatric patients with Turner syndrome. • Relevant progression in childhood is possible in at-risk individuals and warrants close surveillance.

Detection of 15 novel mutations in 52 children from 40 families with the Marfan or Loeys-Dietz syndrome and phenotype-genotype correlations.

We report about 52 pediatric patients of 40 different families with confirmed Marfan syndrome (MFS) in 49 patients and Loeys-Dietz syndrome (LDS) in 3 patients. We found 39 different mutations, 15 of them being novel. Phenotype-genotype correlation in the 49 MFS patients showed that the majority of patients carrying mutations in exons 1-21 had ectopic lens (80%). Patients having mutations in exons 23-32 had a higher probability of aortic root dilation, in 50% even above a z score of 3. We found three children with neonatal MFS form, two of them with novel mutations. Of the three LDS patients, only one presented with the typical phenotype of LDS type 1.

Neurodevelopmental outcome after COX inhibitor treatment for patent ductus arteriosus.

AIM: To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA). METHODS: We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen. RESULTS: Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2wksd) in early (median CRIB 6 and 5, respiratory distress >2 degrees in 36 and 34 infants) and late morbidities (intraventricular hemorrhage >2 degrees in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0wksd) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24months corrected age. CONCLUSION: Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.

Comparison of analgesic/sedative effect of racemic ketamine and S(+)-ketamine during cardiac catheterization in newborns and children.

The hypnotic and analgesic effect of ketamine with maintained spontaneous breathing is used for analgesic/sedative anesthesia without the need of intubation. The intention of this study was to compare the efficacy and side effects of racemic ketamine and its enantiomer S(+)-ketamine during cardiac catheterization in newborns and children. One hundred children (ages 0-11 years) were randomly assigned to groups of equal size. The differences between the racemic ketamine/midazolam and the S(+)-ketamine/midazolam groups were investigated regarding the total dosage of sedative drugs, side effects, and the awakening period. The dosage of S(+)-ketamine (2.28 mg/kg/h) was significantly lower than that needed for racemic ketamine (3.12 mg/kg/h) (p = 0.037) with an analgesic/sedative potency ratio of 1.4:1. Balloon dilatation required significantly higher dosages in both groups (p = 0.043). Significantly more patients were excluded because of ineffective analgesia/sedation or severe side effects in the racemic ketamine group. The awakening period did not show significant differences between the two groups. S(+)-ketamine proved to be a more efficient analgesic/sedative drug in newborns and children. It was shown to be useful in diagnostic and interventional procedures and allows spontaneous breathing. Moderate side effects occurred in both groups; severe side effects seemed to occur more often with the racemic solution.

Knowledge, compliance and practice of antibiotic endocarditis prophylaxis of patients with congenital heart disease.

The aim of this study was to determine the knowledge, compliance, and practice of antibiotic endocarditis prophylaxis (AEP) for patients with congenital heart disease (CHD) during various diagnostic or therapeutic procedures. Patients (296) and their parents were interrogated during a visit with an 18-question survey pertaining to the practice of AEP. Most patients (91.6%) had acyanotic congenital heart disease, usually preoperative (45.3%), or had high risk of infective endocarditis due to previous endocarditis (2.0%), cyanosis (8.4%), or prosthetic valves (5.4%). Potential sources for failure of AEP were (1) no existence of a wallet card (6.8%), no communication between patient and doctor concerning the potential risk of endocarditis during a visit (13.2%), or no sufficient anamnestic inquiry by the physician before procedures were performed (43.2%). The patients underestimated (4.4%) or had no knowledge of the individual risks of endocarditis (37.5%) or underestimated indication for AEP (11.1%). AEP was often not performed at all (60.5%). Bad dental status with no previous dental therapy (35.5%) and a high rate of caries (17.2%) or gingivitis (7.4%) even in young children was frequent. AEP for patients with CHD has not been sufficiently used because of the patient's, and the physician's failure to take the necessary steps, the cardiac diagnosis, or the dental health status. Alternative strategies in prophylaxis for AEP are discussed here.

Primary cardiac tumours: when is surgery necessary?

OBJECTIVE: Primary cardiac tumours are rare. The literature predominantly contains series on myxomas in adults and only a few long-term series that involve the very different primary cardiac tumours in early childhood. As foetal ultrasonography has continued to improve, cardiac tumours are increasingly detected early before significant symptoms develop. It is a challenge for paediatric cardiologists and surgeons to ascertain which patients need surgery and which will benefit from conservative follow-up. METHODS: A retrospective review of a 10-year period revealed 51 tumours in 26 children (median age: 1 month). Analysis was by presentation, location, associated findings, interventions, histological findings, and clinical course. RESULTS: The most common tumours were rhabdomyomas (29), fibromas (nine), teratomas (two), and haemangiomas (two). The tumour location was the right ventricle in 24 and the left ventricle in 22 patients. The symptoms varied between abnormal heart murmur (20), arrhythmia and conduction abnormalities (ten), obstruction of the outflow tract >30 mmHg (nine), severe cyanosis (three) and congestive heart failure (two). Fourteen children with haemodynamic compromises underwent surgery. There was one post-operative death and one heart transplantation after bridging with an assist device. There was no tumour recurrence even when resection was incomplete. Nine of 13 children with rhabdomyomas had spontaneous tumour regression without intervention. CONCLUSIONS: Most of the cardiac tumours in children are benign. Spontaneous regression is possible not only in rhabdomyoma. Surgical intervention is only required for children who develop relevant clinical symptoms. Total resection of the tumour is not the only therapeutic aim; more important is the restoration of the best possible heart function.

At receptor inhibition affects the noradrenaline sensitivity in isolated portal vein of normotensive rat.

Short term treatments of normotensive Wistar Kyoto rats with angiotensin II (ANGII) or in combination with the AT1 receptor antagonist, losartan or PD123319, the AT2 receptor antagonist on systemic arterial blood pressure (MABP) and their influence on noradrenaline sensitivity in isolated mesenteric portal vein were evaluated. ANGII increased MABP as well as the contractile response to noradrenaline in vessels from ANGII-treated animals. MABP and the maximal effect of the concentration response curve for noradrenaline were prevented by losartan. However, PD123319 did not influence the blood pressure, but completely removed the vessels sensitivity to noradrenaline. ANGII combined with the AT1 and/or AT2 receptors blockade completely prevented the pressure response to ANGII, but the concentration response curve for noradrenaline did not differ from the vehicle-treated control curve. In conclusion both AT1- and AT2 receptor activation seems to be important in controlling noradrenaline sensitivity of rat portal vein smooth muscle.

Short treatments of normotensive and hypertensive rats by angiotensin II and nitric oxide inhibitor induce an increase of noradrenaline sensitivity in isolated vena portae preparations.

The aim of the study was to examine the influence of a short-term treatment of conscious Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) by angiotensin II (ANG II) and by ANG II in combination with either l -NAME, HOE 140 or minoxidil on the mean arterial blood pressure (MABP) and the noradrenaline sensitivity in isolated portal vein preparations. MABP was significantly increased by ANG II treatment and ANG II plus l -NAME. However, it was slightly affected by ANG II in association with HOE 140, and significantly lowered by ANG II plus minoxidil. In control animals noradrenaline increased the frequency and the tone of contractile force. While ANG II enhanced the contractile response to noradrenaline, neither in combination with l -NAME, HOE 140 nor minoxidil prevented such an increase in the response to noradrenaline. In the presence of ergotamine, the contractile response to noradrenaline was completely blocked not only in control animals, but also in animals treated with ANG II alone or in combination with minoxidil. However, ergotamine (3 microm) failed to block completely the contractile response to noradrenaline in vessels from animals treated by ANG II in combination with l -NAME or HOE 140. These data suggest that ANG II causes an increase of noradrenaline sensitivity in the isolated portal vein of rat. l -NAME and HOE 140 unmask a contractile response to noradrenaline in the presence of ergotamine which seems to be mediated not only by alpha-adrenoceptors, but may be compensated by an endothelial relaxation.

[The clinical diagnosis of aortic isthmus stenosis]. / Klinische Diagnostik der Aortenisthmusstenose.

BACKGROUND AND OBJECTIVE: Unfortunately, congenital coarctation of the aorta (CoA) is in many cases not diagnosed until adulthood., even though this defect is known to cause serious complications if treated too late. This retrospective study of patients was undertaken to ascertain whether early, exclusively clinical, diagnosis would have been possible. PATIENTS AND METHODS: The case notes of 61 patients with native CoA (n = 45) or restenosis in adulthood after earlier surgical repair (n = 16) were analysed with regard to the findings on physical examination and the patients' symptoms. RESULTS: The patients' age ranged from 15 to 54 years (mean 23 +/- 15.5 years). 48 of 58 patients (83%; incomplete data excluded three patients) had hypertension in the brachial arteries and 50 of 58 (86%) had a pressure difference between the arms. 51 of 53 patients (96%) had a heart murmur, while a pressure gradient between the arms and legs was recorded in in 49 of 51 patients (96%). Notching of the ribs was noted in the chest radiogram of 47 of the 58 patients in whom it was taken. 35 patients had reported one, 23 more than one symptom. CONCLUSION: In all patients (with native CoA or restenosis after surgical repair) it would have been possible to make the correct diagnosis of CoA on the basis of hypertension in the arms, a difference in pulse amplitude and/or a pressure gradient between arms and legs, as well as a cardiac murmur. Normal pressures in ten patients could be explained by marked collateral circulation (rib notching), but even in these patients their symptoms plus at least two other main signs could have provided the correct diagnosis at an earlier time.

AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism.

In the present study we tested the hypothesis whether an angiotensin AT2 receptor-mediated stimulation of the bradykinin (BK)/nitric oxide (NO) system can account for the effects of AT1 receptor antagonism on aortic cGMP described previously in SHRSP. Adult SHRSP were treated for 4 hours with angiotensin II (ANG II) (30 ng/kg per min IV) or vehicle (0.9% NaCl I.V.). Animals were pretreated with vehicle, losartan (100 mg/kg P.O.), PD 123319 (30 mg/kg I.V.), losartan plus PD 123319, icatibant (500 microg/kg I.V.), N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mg/kg I.V.), or minoxidil (3 mg/kg I.V.). Mean arterial blood pressure (MAP) was continuously monitored over the 4-hour experimental period, and plasma ANG II and aortic cGMP were measured by RIA at the end of the study. ANG II infusion over 4 hours raised MAP by about 20 mm Hg. Losartan alone or losartan plus ANG II as well as minoxidil plus ANG II markedly reduced blood pressure when compared to vehicle-treated or ANG II-treated animals, respectively. Plasma levels of ANG II were increased 2-fold by ANG II infusion alone or by ANG II in combination with icatibant, L-NAME, or minoxidil. The increase in plasma ANG II levels was even more pronounced after losartan treatment. Aortic cGMP content was significantly increased by ANG II, losartan, losartan plus ANG II, and minoxidil plus ANG II by 60%, 45%, 68%, and 52%, respectively (P<.05). The effects of ANG II and of losartan plus ANG II on aortic cGMP content were both blocked by cotreatment with the AT2 receptor antagonist PD 123319. Icatibant and L-NAME abolished the effects of ANG II on aortic cGMP. Our results demonstrate the following: (1) ANG II increases aortic cGMP by an AT2 receptor-mediated action because the effect could be prevented by an AT2 receptor antagonist; (2) the effect of ANG II was not secondary to blood pressure increase because it remained under reduction of MAP with minoxidil; (3) losartan increased aortic cGMP most likely by increasing plasma ANG II levels with a subsequent stimulation of AT2 receptors; and (4) the effects of AT2 receptor stimulation are mediated by BK and, subsequently, NO because they were abolished by B2 receptor blockade as well as by NO synthase inhibition.