Marfan syndrome in children and adolescents: predictive and prognostic value of aortic root growth for screening for aortic complications

Background: Marfan Syndrome (MS) is associated with progressive aortic dilation and aortic dissection. Aortic dissection is typically preceded by aortic dilation. The goal of this study is to identify factors associated with faster rates of aortic root dilation in children with MS. Methods: Patients undergoing serial transthoracic echocardiograms (TTE) with MS were retrospectively identified from an institutional database. Those with >2 TTEs over 1 year apart and <21 years of age at first TTE were included. TTEs performed after aortic surgery were excluded. Using multivariable longitudinal linear regression analysis, sex, medication, presence of ectopia lentis, need for scoliosis surgery and infantile type of MS were evaluated for associations with rate of change in aortic root dimension and aortic root z-score over time. Results: Of 240 patients with MS, 146 were included. Median age at first TTE was 8.1 yrs (range 0-20.9 years), median length of follow up 6.5 years (range 1.0-20.1 years), and median number of studies was 8 (range 2-25). Sixty-one percent were male. Of the 146 patients, 123 (84%) were documented to be on medical therapy: 14 angiotensin receptor blocker (ARB), 66 B-Blocker (BB), 10 prior history of both, 5 BB+ARB, 27 were in the Pediatric Heart Network medication trial, 1 ACE inhibitor. Sixteen patients underwent root replacement surgery at a median age of 14.6 years (range 1.8-24). No patients had aortic dissection. Three patients had infantile MS. All of these patients underwent root replacement at 1.8, 2 and 4 years of age. Two underwent subsequent aortic root replacement at 6 and 8 years old. Mean rate of aortic root growth in the cohort was 0.12cm/year, and mean change in z-score was 0.02/year (p=0.23 compared to expected rate of no change). The only variable associated with faster root growth was infantile MS (1.3cm/year, p<0.001; z-score change of 6.9/year, p<0.001). There was no significant difference in the rate of aortic root growth between patients who received therapy with BB vs. ARB vs. BB+ARB. Conclusions: Children with MS did not have a significant change in aortic root z-score over time, and the only factor associated with more rapid aortic root growth was infantile type MS.

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Aortic root growth in children with Marfan syndrome

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(98)80782-1 ◽

1998 ◽

Vol 31 ◽

pp. 30

Author(s):

M. Groenink ◽

L. Rozendaal ◽

M.S. Naoff ◽

R.C. Hennekam ◽

A.A. Hart ◽

...

Keyword(s):

Root Growth ◽

Marfan Syndrome ◽

Aortic Root

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Pregnancy and Aortic Root Growth in the Marfan Syndrome: A Prospective Study

ACC Current Journal Review ◽

10.1016/j.accreview.2005.08.220 ◽

2005 ◽

Vol 14 (9) ◽

pp. 35

Author(s):

L.J. Meijboom ◽

F.E. Vos ◽

J. Timmermans ◽

G.H. Boers ◽

A.H. Zwinderman ◽

...

Keyword(s):

Root Growth ◽

Prospective Study ◽

Marfan Syndrome ◽

Aortic Root ◽

A Prospective Study

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Comment on pregnancy and aortic root growth in the Marfan syndrome: reply

European Heart Journal ◽

10.1093/eurheartj/ehi548 ◽

2005 ◽

Vol 26 (21) ◽

pp. 2346-2347 ◽

Cited By ~ 2

Author(s):

B. J.M. Mulder

Keyword(s):

Root Growth ◽

Marfan Syndrome ◽

Aortic Root

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Aortic Root Dilatation in Children and Adolescents At Al-Hawary General Hospital, & National Benghazi Cardiac Center -Libya

AL-MUKHTAR JOURNAL OF SCIENCES ◽

10.54172/mjsc.v36i4.591 ◽

2021 ◽

Vol 36 (4) ◽

pp. 300-307

Author(s):

Rasmia H. Feituri ◽

Hanan El Megasbi ◽

Mariam M. El maadani ◽

Amal Khazm

Keyword(s):

Aortic Valve ◽

Children And Adolescents ◽

Marfan Syndrome ◽

Aortic Root ◽

Ehlers Danlos Syndrome ◽

Aortic Root Dilatation ◽

Adrenergic Blockers ◽

Danlos Syndrome ◽

Cardiac Center

Isolated dilatation of the aortic root and/or ascending aorta is a rare but well-known cardiovascular manifestation, can be caused by a variety of congenital or acquired conditions; that lead to the weakening of the aortic wall. The study aimed to detect the cause and the rate of the aortic root dilatation in children and adolescents, and to assess the effect of the Beta-adrenergic blockers in preventing further dilatation in the aortic root. A case series study was perform with five years of follow-up at Al-Hawary General Hospital, National Benghazi Cardiac Center. A total of 91 patients were seen with ascending aortic dilatation and/or root dilatation during the period from 6/2016 - 6/2021 included in the study diagnosed by clinical examination, chest x-ray, and echocardiogram. The diagnosis in 34/91(37%) was Tetralogy of fallout (TOF) and truncus arteriosus, 57/91 (63%) was dilated aortic root, 25/57 (44%) bicuspid aortic valve (BAV), 22/57 (38.5%) Marfan syndrome, 4/57(7%) Noonan syndrome, 2/57(3.5%) Turner syndrome, 3/57(5%) Ehlers-Danlos syndrome, 1/57(2%) idiopathic. Follow-up results of three months – five years: 57/91 patients with aortic root dilatation were followed up, none of the Marfan syndrome and Ehlers-Danlos syndrome patients who received beta-blockers had shown progression in the dilatation of the aortic root, and all patients who had bicuspid aortic valve did not show any progression in the dilatation without using medication. Conclusions: Dilated aortic root is a common finding in Marfan syndrome, bicuspid aortic root, and Ehlers-Danlos syndrome, and its progress could be decreased by using beta-adrenergic blockers in rapidly progressing dilation.

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445Effects of losartan and beta-blockers on aortic root dilatation in patients with Marfan Syndrome - results of the extended COMPARE trial

European Heart Journal ◽

10.1093/eurheartj/ehz747.0111 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M M Van Andel ◽

J Jalalzadeh ◽

R Indrakusuma ◽

R Balm ◽

J Timmermans ◽

...

Keyword(s):

Root Growth ◽

Marfan Syndrome ◽

Aortic Root ◽

Favourable Effect ◽

Study Cohort ◽

Aortic Root Dilatation ◽

Dilatation Rate ◽

Β Blocker ◽

Β Blockers

Abstract Introduction Despite several randomized trials, beneficial effects of Losartan and β-blockers in adults with Marfan syndrome (MFS) are not entirely clear. The COMPARE trial previously showed a small but significant beneficial effect of Losartan on top of β-blocker use on aortic root dilatation rate. Yet, this effect was not reproduced by other trials, although in general a favourable effect of Losartan could be demonstrated. All trials in adults with MFS showed lower than expected aortic root dilatation rates, suggesting mildly affected study populations. Therefore we extended the follow-up period of the COMPARE trial up to 10 years and aimed to assess the clinical outcomes of the study cohort, as well as the effect of medication regimes on aortic root dilatation rates in the subgroup of patients with a native aortic root at initial randomization. Methods Patients previously enrolled in the COMPARE trial were retrospectively analyzed. Cardiovascular events (aortic dissections, ruptures and operations) and all-cause mortality were assessed. Individual aortic root dilatation rates were estimated in patients with a native aortic root at time of randomization on the basis of linear regression analysis of multiple transthoracic echocardiogram (TTE) results. Correlations between aortic root dilatation rates and cumulative Losartan or β-blocker treatment days were assessed with Spearman's rho (ρ). Results During a median follow-up of 8.0 years, two dissections and three deaths occurred in the 151 patients with a native aortic root at time of randomization. The 122 patients that were eligible for aortic root dilatation analysis, underwent a median of 6 TTEs. The median aortic root dilatation rate in these patients was 0.28 (interquartile range 0.09 - 0.59) mm/y. These patients were further classified as either patients with a stable aortic root (n=102) or with aortic root growth (n=20), based on the threshold of 0.9 mm per year. Patients with aortic root growth had significantly more aortic root replacements during follow-up (17/20 vs 18/102, P=0.001). Furthermore, aortic root dilatation rate was negatively correlated with the number of Losartan treatment days (ρ=−0.272, P=0.003), β-blocker treatment days (ρ=−0.217, P=0.017) and with the duration of follow-up (ρ=−0.437, P<0.001). Conclusions Our results support previous findings that Losartan and β-blockers appear to be equally effective on aortic root dilatation rate in Marfan Syndrome patients. The low event rate in the long term follow-up of this subgroup of the COMPARE trial represent a relatively mildly affected study population and an aggressive prophylactic surgical regime.

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Influence of Aortic Stiffness on Aortic-Root Growth Rate and Outcome in Patients With the Marfan Syndrome

The American Journal of Cardiology ◽

10.1016/j.amjcard.2018.01.016 ◽

2018 ◽

Vol 121 (9) ◽

pp. 1094-1101 ◽

Cited By ~ 6

Author(s):

Elif Seda Selamet Tierney ◽

Jami C. Levine ◽

Lynn A. Sleeper ◽

Mary J. Roman ◽

Timothy J. Bradley ◽

...

Keyword(s):

Growth Rate ◽

Root Growth ◽

Marfan Syndrome ◽

Aortic Root ◽

Aortic Stiffness ◽

Root Growth Rate

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Semi-automatic quantification of aortic root progressive dilation by automatic co-registration of computed tomography angiograms: a preliminary comparison with manual assessment in Marfan patients

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.224 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

L Dux-Santoy ◽

G Teixido-Tura ◽

A Ruiz-Munoz ◽

L La Mura ◽

F Valente ◽

...

Keyword(s):

Computed Tomography ◽

Growth Rate ◽

Root Growth ◽

Marfan Syndrome ◽

Aortic Root ◽

Public Institution ◽

Maximum Diameter ◽

Automatic Quantification ◽

Root Growth Rate

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Spanish Ministry of Science, Innovation and Universities Instituto de Salud Carlos III Background. Dilation of the aortic root is a key feature of Marfan syndrome and it is related to the occurrence of aortic events and death. On top of maximum diameter, rapid annual growth rate is suggested by guidelines for indication of aortic root replacement. Current gold-standard for aortic root diameter assessment is manual quantification on multiplanar reformatted 3D computed tomography (CT) or magnetic resonance angiogram. However, inter- and intra-observer reproducibility are limited and different measurement methods, i.e. cusp-to-cusp and cusp-to-commissure, may be used in different clinical centres, leading to difficulties in the clinical assessment of progressive dilation. Purpose. We aimed to test whether aortic root growth rate during follow-up can be reliably quantified by semi-automatic co-registration of two CT angiograms. Methods. Seven Marfan syndrome patients, free from previous aortic surgery, with a total of 11 pairs of CT were identified. Manual assessment of six aortic root diameters (right-non coronary -RN- , right-left -RL- and left-non coronary -LN- cusp-to-cusp and R, L and N cusp-to-commissure) was obtained from all CTs by an experienced researcher blind to semi-automatic results. The thoracic aorta and the outflow tract were semi-automatically segmented in the baseline CT and commissure and cusps were manually located. A 10 mm-thick region of interest containing the aortic wall was automatically generated from segmentation boundary. Co-registration was obtained with three, fully-automatic steps. Firstly, baseline and follow-up CT scans were aligned by means of a rigid registration. Then, scans were co-registered with multi-resolution affine followed by b-spline non-rigid registrations based on mutual information metric. The transformation pertaining to the location of baseline commissure and cusps points was used to locate the same points in the follow-up scan (Fig. 1 top). Results. Follow-up duration was 35 ± 22 (range 12-70.3) months. Automatic quantification of diameter growth during the follow-up was obtained in 62 out of 66 (94%) diameter comparisons. High Pearson correlation coefficients (R) and ICC were found between manual and semi-automatic assessment of growth rate, both for cusp-to-cusp and cusp-to-commissure diameters: R = 0.727 and ICC = 0.678 for RN; R = 0.822 and ICC = 0.602 for RL; R = 0.648 and ICC = 0.668 for LN; R = 0.726 and ICC = 0.711 for R; R = 0.911 and ICC = 0.895 for L and R = 0.553 and ICC = 0.482 for N. Scatter and Bland-Altman plots for all growth rates (Fig. 1) confirmed very good correlation (R = 0.810) but a slight tendency (R=-0.270) for underestimation at high growth rate. No correlation was found between follow-up duration and difference between techniques (R = 0.06). Conclusions. Semi-automatic quantification of aortic root growth rate by co-registration of pairs of CT angiograms is feasible for follow-up as short as one year. Larger studies are needed to confirm these preliminary data. Abstract Figure. CT measurements. Automatic vs manual.

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