THE AORTA IN TURNER SYNDROME. Dr. L. Demulier Annual meeting of the BWGACHD March 11 th 2016
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1 THE AORTA IN TURNER SYNDROME Dr. L. Demulier Annual meeting of the BWGACHD March 11 th 2016
2 TURNER SYNDROME : INTRODUCTION Prevalence = 1/2000 life born girls Partial/complete deletion X-chromosome Multiple karyotypes ± cell line mosaicism Small stature / estrogen deficiency / infertility Dysmorphic features Highly variable phenotype (diagnostic delay) Multisystemic manifestations Congenital / acquired CV disease Mortensen et al. Endocrine Reviews 2012
3 EXCESS PREMATURE MORTALITY & MORBIDITY Risk of premature death x 3 : CVD = n 1 Life expectancy : 10y 50% of morbidity = CVD High early life disease burden Mortensen et al. Endocrine Reviews 2012
4 IMPORTANCE OF ACQUIRED CV DISEASE Schoemaker et al. J Clin Epidemiol 1998 Mortensen et al. Endocrine Reviews 2012
5 CARDIOVASCULAR ANOMALIES : CONGENITAL AND ACQUIRED Mortensen et al. Endocrine Reviews 2012
6 CONGENITAL HD: BICUSPID AORTIC VALVE (15-30%) ⅓ 95% Sachdev et al. Jacc 2008 ⅔ Echo ± MRI NIH study in 253 asy TS pts (7-67y) 95% Type 1 BAV (vs 60-70%) 45% AR - 15% moderate-severe ; AS rare Diagnosis: 89% echo / 99% MRI Association with webbed neck (45%), aortic coarctation (22%), 45 X0
7 BAV AND AORTIC DILATION ARD: BAV 25% - TAV 5% Sachdev et al. Jacc 2008 Riti Mahadevia et al. Circulation. 2014
8 PARTIAL CUSP FUSION AND AORTIC DILATION IN TS Olivieri et al. Circ Cardiovasc Imaging 2013
9 CONGENITAL HD : THORACIC VASCULAR ABNO ELONGATION TRANVERSE ARCH (49%) COARCTATION (up to 17%) Association with BAV Need for repair +/- 50% Frequent association with ETA KINKING ARCH LUSORIAN ARTERY (8%) PERSISTENT LEFT SCV (8-13%) PAPVR (13-15%) Associated with: Karyotype 45,X Neck webbing Shield like chest Mortensen et al. Endocrine Reviews 2012 Ho et al. Circulation y TS (45,X)
10 HD EFFECTS OF ALTERED ARCH GEOMETRY : CFD Wittberg, Backeljauw et al. Biomech Model Mechanobiol 2015
11
12 ASSOCIATION HYPERTENSION AND ARCH MORPHOLOGY
13 HEMODYNAMIC CASE STUDY : 19y TS CFD ANALYSE - courtesy of J. Bols 4D FLOW - courtesy of D. Devos Radiology Dept UZG
14 ACQUIRED CARDIOVASCULAR ANOMALIES Mortensen et al. Endocrine Reviews 2012
15 IS THIS ASCENDING AORTA DILATED?
16 ABSOLUTE VERSUS BSA-INDEXED AORTIC DIAMETER 48y - mosaic TS Ascending aorta diameter = 28 mm Never GH treatment 132 cm 47 kg BSA 1.27 m² Aortic size index (ASI) = 22 mm/m²
17 IMPORTANCE OF PROPORTIONS
18 ABSOLUTE DIAMETER = BAD DISCRIMINATOR IN TS Ostberg et al. JCEM 2004
19 CAREFUL WITH GUIDELINE EXTRAPOLATIONS
20 DEFINITION OF AORTIC DILATION? comparison to age-matched controls (> 95th percentile) correction for BSA or height Mortensen et al. Endocrine Reviews 2012
21 TURNER SPECIFIC REFERENCE VALUES BSA corrected reference z-scores for echo measurements 481 healthy TS pts (age 2-70 ; av 25) Excl : BAV / dissection / operation / cath interv / sev AR /AS Quezada et al. Am J Med Genet Part A
22 DETERMINANTS OF AORTIC DILATION BAV Mortensen et al. JCMR 2013
23 AORTIC DIAMETER PREDICTION MODEL INPUT RISK FACTORS Values Antihypertensive treatment (yes/no) 1 (0/1) Coarctation of the aorta (yes/no) 0 (0/1) Aortic valve morphology 1 (0/1) Body surface area (m2) 1,5 Age (years) 30 Diastolic blood pressure (mm Hg) 85 No antihypertensive treatment = 0 No aortic coarctation = 0 Tricuspid aortic valves = 0 Body surface area = * (weight)0.425 * (height) ,0 40,0 35,0 Predicted diameter of the thoracic aorta in Turner syndrome, at 9 separate positions from aortic sinuses to distal descending thoracic aorta Mean predicted dimameter (mm) with 95% prediction limits, and please see above for measurement positions. 30,0 25,0 20,0 15,0 10,0 5,0 0, Mortensen et al. JCMR 2013 (
24 Mortensen et al. JCMR 2011/ mm/y (0,07 mm/y) BAV: 0,64 mm/y (sinus)
25 ACQUIRED CARDIOVASCULAR ANOMALIES Mortensen et al. Endocrine Reviews 2012
26 50j TS (iso X) - BAV - AHT - AoC- syncope & acute abdo pain Type A dissection R/ Bentall procedure & aortic arch replacement
27 ACQUIRED HD : AORTIC DISSECTION Lifelong risk ~ 1,4% Median age 35y (18-61y) Gravholt et al. Cardiol Young 2006 Retrospective study Denmark/Sweden (33y) 63% 37%
28 IS THERE A CRITICAL DIAMETER?
29 PROSPECTIVE NIH study FU period 3y 166 adult TS 26 healthy age matched control volunteers ( 18y) MRI assessment ascending/descending aortic diameter (AD at RPA) 95 th percentile AD controls : 3,4 cm aortic size index 2,0 cm/m² (BSA) 3 aortic dissections ASI > 2,5 cm/m² (99 th percentile) ; BAV ⅔ ; ETA ⅓ TS pts with ASI > 2,5 cm/m² developped aortic dissection / 3y ASI > 2,5 cm/m² = cut off for extreme dilation for intervention? Matura et al. Circulation 2007
30
31 Median age 65 y ; 67% hypertension ; 36% smokers Exclusion criteria : coarctation
32 FOCUS ON MULTIPLE RISK FACTORS IN TS
33 CHD only 35% TS only 11% CHD and HTN 40% HTN only 14% Literature review ( ) : 85 cases Poorly documented! 80% 45,X 20% Mosaic (49 karyotypes) 69% CHD (out of 87%) 47% coarctation 6/85 AD after ART Carlson M, Silberbach M. J Med Genet 2007 RISK MARKERS FOR AORTIC DISSECTION o Age o Hypertension o Aortic dilation o BAV o Coarctation/obstr ao arch o Karyotype 45,X o Pregnancy o Aortic interventions Mortensen et al. Endocrine Reviews 2012
34 Prospective study in 49 TS pts compared to lean and obese controls Major finding : childhood-onset increased vessel stiffness (as early as 9y) Increased risk for aortic dilation / dissection?
35 International TS Aortic Dissection Registry (ITSAD registry) 20 aortic dissections 1 coarc stent 19 spont 18 BAV Mean age 31,5y Ao diameters in 15/19 17/20 Type A Mean ASI 2,7 cm/m² ASI > 2,5 cm/m²: cut off intervention? 5 obst arch 1 no CHD 1 pregnancy (ART) Carlson et al. Circulation 2012
36 Chevalier et al. JCEM 2011
37 CASE REPORTS OF AORTIC DISSECTION DURING PREGNANCY MATERNAL MORTALITY 75% Chevalier et al. JCEM 2011
38 o Increased risk of aortic dissection in TS patients o Risk with BAV coarctation AHT o highest risk if aortic dilation (index voor BSA!) o aortic diameter 27 mm/m² : consider prophylactic sugery
39 CONTRA-INDICATIONS FOR PREGNANCY o aortic diameter > 35 mm o aortic diameter > 25 mm/m² o progression ao diam > 10%/y o coarctation aorta o uncontrolled AHT o history of aortic surgery o history of aortic dissection o BAV = risk factor (no CI) ABSOLUTE o aortic diameter > 20 mm/m² o significant CV anomaly on cardiac MRI RELATIVE o Turner syndrome Chevalier et al. JCEM 2011 ASRM Practice Committee. Fertil Steril 2012
40 o TS frequently associated with congenital / acquired CV disease o Aortic disease is an important cause of early excess mortality o Aortic diameters should be corrected for BSA o Echocardiography and MRI are mandatory in every patient o Increased risk of aortic dissection especially during pregnancy o Further research is needed to determine who is at highest risk o Multidisciplinary FU in a specialized Turner clinic is recommended
41 THANK YOU FOR YOUR ATTENTION!
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