Veronika Stark

Retrospective analysis of the effect of angiotensin II receptor blocker versus β-blocker on aortic root growth in paediatric patients with Marfan syndrome

Objectives Cardiovascular pathology, including aortic root dilation at the level of sinus of Valsalva (SV), is one of the major causes of morbidity in paediatric patients with Marfan syndrome (MFS). β-Blocker (BB) is well established to slow aortic dilation in MFS. Less is known about the effectiveness of angiotensin II receptor blocker (ARB) on aortic dilation in paediatric patients with MFS. Methods 215 patients with MFS (9.01±5.7u2005years) were subject to a standardised diagnostic programme. Aortic root dilation was evaluated and followed up by echocardiography. In 48 cases, BB and ARB effects on aortic root dilation were evaluated. Effect of treatment was measured by comparison of z scores of SV before and after treatment initiation. Results Treatment by ARB and BB leads to significant reduction of SV dilation (p<0.05). The deviation of SV enlargement from normal as expressed by the rate of change in z scores was significantly reduced by a mean difference of −0.56±0.71 z scores (p<0.001) under ARB therapy and by a mean difference of −0.35±0.68 z scores (p<0.05) under BB therapy. The prophylactic effect of ARB and BB on aortic root dilation is similar in both groups (p>0.05). Conclusions Both concepts lead to a significant reduction of SV dilation. The effect of ARB and BB is similar. This is the first study concerning the comparison of ARB and BB in previously untreated paediatric patients with MFS. The results of the study show that both treatment strategies are beneficial in paediatric and adolescent patients.

Impact of Age and Gender on Cardiac Pathology in Children and Adolescents With Marfan Syndrome

Abstract Cardiac pathologies are the major aspect in the treatment strategies for Marfan syndrome (MFS). In this progressive disease, less is known about manifestations and progression of cardiovascular symptoms in children. To define a certain decision regarding therapeutic options, knowledge concerning the onset of cardiovascular findings is essential. From 1998 to 2011, suspected pediatric Marfan patients were subjected to a standardized diagnostic program. Cardiovascular findings were analyzed in terms of age at first clinical manifestation, prevalence and gender differences, morbidity, mortality, and treatment. Marfan syndrome was diagnosed in 82 patients (46 boys; mean age at diagnosis, 9.0xa0±xa05.7xa0years). At first presentation, aortic root dilation was found in 56xa0% of patients, mitral valve prolapse in 31xa0%, whereas pulmonary artery dilation was detected in 22xa0% and tricuspid valve prolapse in only 17xa0% of patients. Aortic (2.5xa0%) and mitral valve regurgitations (22xa0%) are significantly correlated with aortic root dilation (pxa0<xa00.01) and mitral valve prolapse (pxa0<xa00.05) but without relevant progression during childhood. Prophylactic medication was initiated for 42xa0% of the patients (mean age, 8.0xa0±xa04.5xa0years) because of progressive aortic root dilation. Aortic dissection did not appear. Aortic root surgery was needed for 4xa0% of the patients. Gender-specific differences in cardiovascular findings, progression of disease, or treatment did not appear. Comparable with adults, aortic root dilation is the most frequent cardiovascular finding in children and associated with relevant morbidity, whereas aortic and mitral valve regurgitation are of minor clinical relevance. Manifestation at an early age and slow progression of cardiovascular findings underscore the necessity of repeated echocardiographic examinations for early diagnosis and start of prophylactic treatment.

The Kid-Short Marfan Score (Kid-SMS) - an easy executable risk score for suspected paediatric patients with Marfan syndrome

Due to age‐dependent manifestations, diagnosis of Marfan syndrome (MFS) in children and adolescents is sophisticated. Although revised Ghent criteria is a major step forward, its utility in children is still restricted due to expensive and technically advanced diagnostics. As early diagnosis submits long‐term benefits concerning prognosis, the need of an appropriate diagnostic tool for risk stratification of suspected paediatric patients with Marfan is justified.

Health-related quality of life is unimpaired in children and adolescents with Marfan syndrome despite its distinctive phenotype

Marfan syndrome (MFS) is a progressive, life‐threatening genetic disorder of the connective tissue, which causes impaired quality of life (QoL) in adults. This study investigated the quality of life in children and adolescents, taking into account their gender, age and how MFS affected their organs.

Pediatric Patients with Marfan Syndrome: Frequency of Dural Ectasia and its Correlation with Common Cardiovascular Manifestations

PURPOSEnMarfan syndrome (MFS) is a genetic disorder of the connective tissue. Aortic root dilation is a main criterion of the Ghent Nosology. Dural ectasia and the presence of mitral valve prolapse (MVP) contribute to its systemic score. The purpose of this study was to investigate the frequency of dural ectasia and its correlation with cardiovascular manifestations in a pediatric study population.nnnPATIENTS AND METHODSn119 pediatric patients with confirmed or suspected MFS were examined in the local Marfan Clinic. 31 children with MFS who underwent magnetic resonance imaging (MRI) were included. Each patient was evaluated according to the Ghent nosology. Echocardiography was used to measure the aortic root diameter and assess the presence of MVP and mitral regurgitation. Z-scores were calculated for the evaluation of the aortic root diameters. MRI was performed to determine the dural sac ratio (DSR).nnnRESULTSnThe prevalence of dural ectasia was 90.3u200a%, of aortic root dilation 32.2u200a%, of MVP 64.5u200a% and of mitral regurgitation 51.6u200a%. DSR at L5 correlated with the intraindividual z-scores (slope, 3.62u200a±u200a1.5 [0.56; 6.68]; ru200a=u200a0.17; pu200a=u200a0.02; Fu200a=u200a5.84). Z-scores ≥u200a2 were accompanied by dural ectasia in 100u200a%, MVP in 95u200a% and mitral regurgitation in 100u200a% of cases. MVP was accompanied by mitral regurgitation in 70u200a% of cases.nnnCONCLUSIONnAs the examined cardiac manifestations show a coincidence with dural ectasia in 95u200a-u200a100u200a% of cases, MRI for diagnostic dural sac imaging should be reserved for MFS suspicions with the absence of those manifestations in order to establish the diagnosis according to the Ghent criteria. Thus, the present study supports the recent downgrading of dural ectasia to a contributor to the systemic score.

The Pulmonary Artery in Pediatric Patients with Marfan Syndrome: An Underestimated Aspect of the Disease

Aortic root dilatation and its complications are known to be the most important and life limiting features in patients with Marfan syndrome (MFS). Since monitoring of patients, preventive medical and surgical treatments are available nowadays, other MFS pathologies are becoming more relevant for the outcome of the disease. Main pulmonary artery (MPA) dilatation is a cardiac finding, which has not been fully investigated in children. Due to the similarities in tissue composition of the aortic and pulmonary root, MPA dilatation may cause complications and require treatment. In addition, it may be a predictor for severe connective tissue involvement. We retrospectively examined 135 pediatric patients with MFS. 8.1% showed MPA dilatation. MPA dilatation was associated with earlier occurrence of aortic dilatation, mitral valve prolapse, and systemic manifestations of MFS compared with patients without MPA dilatation (pu2009<u20090.05). The presence of MPA dilatation was also associated with a higher incidence of ectopia lentis (pu2009<u20090.05). Medical treatment was started earlier in MPA dilatation patients than in those without (pu2009<u20090.05). We conclude that MPA dilatation is a sign of more severe vascular and connective tissue involvement. Regular examination of the pulmonary artery is essential in MFS to avoid complications. As medical treatment of life threatening MFS events has improved, other features of MFS need to be investigated to improve quality of life.

Kid-Short Marfan Score (Kid-SMS) Is a Useful Diagnostic Tool for Stratifying the Pre-Test Probability of Marfan Syndrome in Childhood

Due to age dependent organ manifestation, diagnosis of Marfan syndrome (MFS) is a challenge, especially in childhood. It is important to identify children at risk of MFS as soon as possible to direct those to appropriate treatment but also to avoid stigmatization due to false diagnosis. We published the Kid-Short Marfan Score (Kid-SMS) in 2012 to stratify the pre-test probability of MFS in childhood. Hence we now evaluate the predictive performance of Kid-SMS in a new cohort of children. We prospectively investigated 106 patients who were suspected of having MFS. At baseline, children were examined according to Kid-SMS. At baseline and follow-up visit, diagnosis of MFS was established or rejected using standard current diagnostic criteria according to the revised Ghent Criteria (Ghent-2). At baseline 43 patients were identified with a risk of MFS according to Kid-SMS whereas 21 patients had Ghent-2 diagnosis of MFS. Sensitivity was 100%, specificity 77%, negative predictive value 100% and Likelihood ratio of Kid-SMS 4.3. During follow-up period, three other patients with a stratified risk for MFS were diagnosed according to Ghent-2. We confirm very good predictive performance of Kid-SMS with excellent sensitivity and negative predictive value but restricted specificity. Kid-SMS avoids stigmatization due to diagnosis of MFS and thus restriction to quality of life. Especially outpatient pediatricians and pediatric cardiologists can use it for primary assessment.