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The Dilated Aorta: What Disease and How to Evaluate
Alan C. Braverman, MD, FACC
Alumni Endowed Professor in Cardiovascular Diseases Professor of Medicine
Director, Marfan Syndrome Clinic, Barnes-Jewish Hospital Director, Inpatient Cardiology Firm
Washington University School of Medicine, St. Louis, MO Chair, Professional Advisory Board, The Marfan Foundation
Disclosure
§ Nothing relevant to disclose
From: Braverman AC, Thompson R, Sanchez L. Diseases of the Aorta, Chapter 60. In, Bonow RO, Mann DL, Zipes DP, Libby P. Braunwald’s Heart Disease, 9th Edition. pp. 1309-1337 . Elsevier, Philadelphia. 2011
Why do I have a dilated aorta?
Why did I have an aortic dissection?
Am I at risk for an aortic aneurysm or dissection?
Clinicians Concerns in Thoracic Aortic Diseases
1. Accurate diagnosis of the underlying disease
2. Pharmacologic therapy
4. Lifestyle modification
3. Timing of aortic surgery
Thoracic aortic
aneurysm
Genetically triggered syndrome
Degenerative
Inflammatory Mechanical
Infectious
Marfan
Loeys-Dietz
FTAA
BAV aortopathy
vEDS
Turner syndrome
Others…
HTN
atherosclerosis
Giant cell arteritis
Non-specific aortitis
Takayasu’s arteritis
Reiter’s syndrome
Kawasaki disease
Behcet’s syndrome
Aortic dissection
Trauma
Bacterial
Staph, Salmonella
Syphilis
Fungal
Infected TEVAR
• Marfan syndrome
• Loeys-Dietz syndrome
• Familial thoracic aortic aneurysm/dissection
• Vascular Ehlers-Danlos syndrome • Bicuspid aortic valve aortopathy
• Turner Syndrome
Genetically Triggered Thoracic Aortic Disease
• Marfan syndrome
• Loeys-Dietz syndrome
• Familial thoracic aortic aneurysm/dissection
• Vascular Ehlers-Danlos syndrome • Bicuspid aortic valve aortopathy
• Turner Syndrome
Genetically Triggered Thoracic Aortic Disease
• Marfan syndrome
• Loeys-Dietz syndrome
• Familial thoracic aortic aneurysm/dissection
Genetically Triggered Thoracic Aortic Disease
The different disorders leading to thoracic aortic
aneurysm have variable natural histories and different
inherent risks of aortic and branch vessel aneurysm and
dissection.
Importance of a Correct Diagnosis:
What are the Red Flags in Diagnosis of TAA Disease?
1. Family History:
TAA, aortic dissection
Bicuspid aortic valve
Cerebral aneurysm
Features of connective tissue disease
2. History and Physical examination
Marfan syndrome features FBN1
Marfan Syndrome
¨ Autosomal Dominant Connective Tissue Disorder
¨ FBN1 mutation (fibrillin-1) ¨ Incidence: 1:5000 – 1:10,000 ¨ 25% Cases: Spontaneous Mutation ¨ Multisystem manifestations
Marfan Syndrome: Importance of Accurate Diagnosis
¨ May be diagnosed at birth or not recognized until late in life
¨ If unrecognized and untreated, the
average age of death in Marfan syndrome is ~45 years old.
¨ Aortic Complications (Aortic Dissection
and Aortic Regurgitation) are responsible for 90% of the Morbidity and Mortality in Marfan syndrome.
¨ Careful assessment and long term follow-
up are critical to the outcome of patients with Marfan syndrome.
¨ Median probability of survival is now into the 70’s.
Molecular Genetics of the Marfan Syndrome
FBN1 • 65 Exons spanning 235 kb of genomic DNA
• encodes a 350 kDa glycoprotein—fibrillin-1
• most mutations occur within the 47 tandemly repeated EGF-like domains,
--disrupts cysteine residues or Ca++ binding sites
~3200 mutations reported in FBN1 on Chromosome 15 causing Marfan syndrome.
What Does Marfan Syndrome Look Like?
What Does Marfan Syndrome Look Like?
Marfan Syndrome: Skeletal Features
Marfan Syndrome: Skeletal Features
• Facial appearance (dolichocephaly, malar hypoplasia, enophthalmos, retrognathia, down-slanting palpebral fissures)
Highly arched palate with dental crowding
Skeletal System
Sponseller PD, et al. J Bone Joint Surg Am 2010:92:1868-75
Ocular System
Minor Criteria: ¨ Abnormally flat cornea (as
measured by keratometry) ¨ Increased axial length of globe
(as measured by ultrasound)
¨ Hypoplastic iris or hypoplastic ciliary muscle causing decreased miosis
Major Criterion:
• Ectopia Lentis
Feature Value
Wrist and Thumb sign 3 Wrist or Thumb sign 1 Pectus Carinatum deformity 2 Pectus Excavatum or chest asymmetry 1 Hindfoot deformity 2 Plain flat foot (pes planus) 1 Pneumothorax 2 Dural Ectasia 2 Protrusio acetabulae 2 Reduced US/LS ratio and increased arm span/height 1 Scoliosis or thoracolumbar kyphosis 1 Reduced elbow extension 1 3 or 5 facial features 1 Skin striae 1 Myopia (>3 diopters) 1 Mitral valve prolapse 1
Systemic Features Scoring (> 7 points)
The Revised Ghent Nosology for the Marfan syndrome.
Bart Loeys, Harry Dietz, Alan C. Braverman, Bert Callewaert, Julie De Backer, Richard Devereux, Yvonne Hilhorst, Guillaume Jondeau, Laurence Faivre, Diane Milewicz, Reed
Pyeritz, Paul Sponseller, Paul Wordsworth, Anne De Paepe. J Med Genet 2010;47:476-485.
In the absence of family history:* (1) Ao (Z≥2) + EL = MFS (2) Ao (Z≥2) + FBN1 = MFS (3) Ao (Z≥2) + Syst (≥7pts) = MFS (4) EL + FBN1 with known Ao = MFS
In the presence of family history:* EL + FH of MFS (as defined above) = MFS Syst (≥7 pts) + FH of MFS (as defined above) = MFS Ao (Z≥3) + FH of MFS (as defined above) = MFS
absence of features suggesting an alternative disorder—i.e. LDS,SGS,FTAA
What are the Red Flags in Diagnosis of TAA Disease?
1. Family History:
TAA, aortic dissection
Bicuspid aortic valve
Cerebral aneurysm
Features of connective tissue disease
2. History and Physical examination
Marfan syndrome features
Bifid uvula, cleft palate
Velvety skin, visible veins
Hypertelorism, clubbed feet
Loeys-Dietz
TGFBR1/2
Loeys-Dietz Syndrome: TGFBR1 and TGFBR2 mutations
Hypertelerism Bifid/broad uvula Arterial tortuosity
Aortic aneurysm and dissection Branch vessel aneurysms
Craniosynostosis Club feet
Cutaneous features Blue sclera Scoliosis
Loeys-Dietz Syndrome
Aneurysm Syndromes Caused by Mutations in TGFB Receptors. Loeys et al. NEJM 2006;355:788
Correlation exists between the severity of craniofacial features and severity of cardiovascular phenotype and age of 1st cardiovascular event
What are the Red Flags in Diagnosis of TAA Disease?
Clues from Imaging Studies:
Arterial tortuosity
ectasia of arteries
branch vessel dilatation or dissection
LDS, SMAD3, TGFB2
Skeletal Features in Loeys-Dietz Syndrome
Overlap with Marfan syndrome
joint laxity, pectus deformity, scoliosis, pes planus Distinct from Marfan syndrome
contractures of feet (talipes equinovarus) and fingers (campylodactyly)
Chiari malformations
cervical spine defects or instability/subluxation
Abnormalities of the Uvula in Loeys-Dietz Syndrome
Bifid uvula, trilobed uvula, broad uvula, prominent raphe
Cutaneous Features in Loeys-Dietz Syndrome
Velvety, translucent skin with visible veins
Easy bruising,
Wound healing may be delayed. Some scars dystrophic
What are the Red Flags in Diagnosis of TAA Disease?
1. Family History:
TAA, aortic dissection
Bicuspid aortic valve
Cerebral aneurysm
Features of connective tissue disease
2. History and Physical examination
Marfan syndrome features
Bifid uvula, cleft palate
Velvety skin, visible veins
Hypertelorism, club feet
Loeys-Dietz
TGFBR1/2
What are the Red Flags in Diagnosis of TAA Disease?
1. Family History:
TAA, aortic dissection
Bicuspid aortic valve
Cerebral aneurysm
Features of connective tissue disease
2. History and Physical examination
Marfan syndrome features
Bifid uvula, cleft palate
Velvety skin, visible veins
Hypertelorism, clubfeet
Loeys-Dietz
TGFBR1/2
TGFB2, TGFB3
1. Family History:
TAA, aortic dissection
Bicuspid aortic valve
Cerebral aneurysm
Features of connective tissue disease
2. History and Physical examination
Marfan syndrome features
Bifid uvula, cleft palate
Velvety skin, visible veins
Hypertelorism, club feet
Loeys-Dietz
TGFBR1/2
TGFB2/3 Osteoarthritis SMAD3
What are the Red Flags in Diagnosis of TAA Disease?
1. Family History:
TAA, aortic dissection
Bicuspid aortic valve
Cerebral aneurysm
Features of connective tissue disease
2. History and Physical examination
Marfan syndrome features
Bifid uvula, cleft palate
Velvety skin, visible veins
Hypertelorism, club feet
Livedo reticularis, PDA, premature CAD, CVD, Moya-Moya
FTAA/D ACTA2
MYH11 PDA
What are the Red Flags in Diagnosis of TAA Disease?
Familial Thoracic Aortic Aneurysm and Dissection FTAA/D
Molecular Genetics in FTAA/D Syndromes: Gene Panels • ACTA2 SMC α-actin (10-14% of FTTA/D)
Associated with livedo reticularis, PDA, BAV, iris flocculi, cerebral aneurysms, premature CAD
• MYH11 (myosin heavy chain 11) 16p13.13-p13.12 (1%)
Associated with patent ductus arteriosus, livedo reticularis, BAV
• MLCK (myosin light chain kinase) (1%)
• SMAD3 (aneurysms and premature osteoarthritis) 15q22.33 (3%)
• TGFBR1 (2%);
• TGFBR2 (4%)
• TGFB2-ligand loss of function mutations
• TGFB3
• COL3A1; COL5A1, SKI, FLNA, SLC2A10
• More to come….
20% of individuals with TAA or Type A aortic dissection have an affected 1st degree relative. Coady et al. Arch Surg 1999; 134:361-7
Familial Thoracic Aortic Aneurysm and Dissection FTAA/D
Molecular Genetics in FTAA/D Syndromes: Gene Panels • ACTA2 SMC α-actin (10-14% of FTTA/D)
Associated with livedo reticularis, PDA, BAV, iris flocculi, cerebral aneurysms, premature CAD
• MYH11 (myosin heavy chain 11) 16p13.13-p13.12 (1%)
Associated with patent ductus arteriosus, livedo reticularis, BAV
• MLCK (myosin light chain kinase) (1%)
• SMAD3 (aneurysms and premature osteoarthritis) 15q22.33 (3%)
• TGFBR1 (2%);
• TGFBR2 (4%)
• TGFB2-ligand loss of function mutations
• TGFB3
• COL3A1; COL5A1, SKI, FLNA, SLC2A10
• More to come….
20% of individuals with TAA or Type A aortic dissection have an affected 1st degree relative. Coady et al. Arch Surg 1999; 134:361-7
In many families with TAA aneurysm or dissection, a specific mutation in one of these genes will not be present.
What are the Red Flags in Diagnosis of TAA Disease?
Clues from Imaging Studies:
56 year old woman with acute type A aortic dissection
What are the Red Flags in Diagnosis of TAA Disease?
Clues from Imaging Studies:
Lumbosacral Dural Ectasia
MFS FBN1
LDS TGFBR1/2, TGFB2, SMAD3
vEDS COL 3A1
What are the Red Flags in Diagnosis of TAA Disease?
Clues from Imaging Studies:
Pattern of Aortic Dilatation SOV, Aortic Root
MFS, LDS, SMAD3, TGFB2, others
What are the Red Flags in Diagnosis of TAA Disease?
Clues from Imaging Studies:
Pattern of Aortic Dilatation Ascending Aorta
BAV disease
ACTA2
MYH11
overlap
“Medical Management” of Thoracic Aortic Aneurysm Disease
Pharmacotherapy Education Advocacy Lifestyle modification Exercise guidelines Pregnancy guidelines
• Theoretical benefits of pharmacologic therapy.
Lower BP, less aortic stress, anti-inflammatory
• Animal (mouse) model data.
• Studies in humans are very limited.
Controlling HTN, smoking cessation, and treating hyperlipidemia is recommended for patients with TAA disease.
Medical Therapy in Thoracic Aortic Aneurysm Disease: Caveats
Progression of Aortic Dilatation and the Benefit of Long-Term Beta-Adrenergic Blockade in Marfan’s Syndrome
Shores et al. New Engl J Med 1994;330:1335-1341.
Beneficial Effects of Beta Blockers:
• Decreased rate of aortic root enlargement • Fewer patients developed aortic dissection
TAD guidelines recommend beta blocker therapy in patients with Marfan syndrome to reduce the rate of aortic dilatation.1
1Hiratzka LF, et al. Guidelines for the diagnosis and management of patients with thoracic aortic disease. J Am Coll Cardiol. 2010;55:e27-e129.
TGFβ stimulates both canonical (SMAD) and non-canonical pathways. Perinatal antagonism of TGF-β using neutralizing antibody rescues pathologic phenotype in Marfan mice. AT1-receptor blockade (using angiotensin receptor blocker Losartan) induces a decrease in TGF-β signaling.
Doyle JJ, Gerber EE, Dietz HC. FEBS Letters 2012;586:2003-15
Losartan, an AT1 Antagonist, Prevents Aortic Aneurysm in a Mouse Model of Marfan Syndrome
Habashi JP, Judge DP et al. Science 2006;312:117-121
ARB Therapy in Marfan Syndrome Brooke et al. NEJM 2008;358:2787
17 pts aged 14 months to 16 years who had received ARB therapy for >1 year.
These pts had severe aortic enlargement (mean z-score of 7.2 at time of ARB therapy).
Pts on ARB therapy had significant decrease in the rate of change of aortic root diameter (3.5 mm/yr vs. 0.5 mm/yr).
Change in Aortic-Root Diameter Standardized According to the Time of Initiation of Therapy with an Angiotensin II–Receptor Blocker (ARB).
ARB Trials in Marfan Syndrome
Randomized Trial of Atenolol Versus Losartan in Children and Young Adults
with Marfan Syndrome
Ronald V. Lacro, Harry C. Dietz, Lynn A. Sleeper, Anji T. Yetman, Timothy J. Bradley, Steven D. Colan, Gail D. Pearson, Elif Seda Selamet Tierney, Jami C. Levine, Andrew M. Atz, D. Woodrow Benson, Alan C. Braverman, Shan Chen, Julie De Backer, Bruce D. Gelb, Paul D. Grossfeld, Gloria L.
Klein, Wyman W. Lai, Aimee Liou, Bart L. Loeys, Larry W. Markham, Aaron K. Olson, Stephen M. Paridon, Victoria L. Pemberton, Mary Ella Pierpont,
Reed E. Pyeritz, Elizabeth Radojewski, Mary J. Roman, Angela M. Sharkey, Mario P. Stylianou, Stephanie Burns Wechsler, Luciana T. Young,
Lynn Mahony for the Pediatric Heart Network Investigators
Losartan reduces aortic dilatation rates in adults with Marfan syndrome: a randomized controlled trial.
Groenink M et al. Eur Heart J 2013:34;3491-50.
Multicenter, open-label, RCT with blinded assessments Losartan added to prior treatment in operated and unoperated Marfan patients (72% on beta blocker therapy) 233 patients (38 + 13 years, 47% females) followed 3.1 + 0.4 years
Aortic root size ~44 mm
116 treated with losartan; 117 treated with no add’l treatment 100 mg in 63 pts (54%) 50 mg in 34 pts (29%) 15% patients stopped losartan due to side effects
Losartan reduces aortic dilatation rates in adults with Marfan syndrome: a randomized controlled trial.
Groenink M et al. Eur Heart J 2013:34;3491-50.
Outcome MRI
(change in mm/3 years)
Control N=105
Losartan N=113 P-value
Aortic root 1.35 + 1.55 0.77 + 1.36 0.014 Ascending
aorta 0.85 + 1.23 0.78 + 1.32 0.726
Aortic arch 0.61 + 1.35 0.52 + 1.37 0.598 Descending aorta (PA) 0.72 + 1.40 0.54 + 1.40 0.366
Outcome TTE
Aortic root 1.93 + 1.39 1.34 + 1.51 0.021
19 pts underwent prophylactic aortic root replacement. No difference between groups.
Ha et al. Radiographics 2007
Prophylactic Aortic Root Surgery in the Marfan Syndrome
When the aortic root reaches 5 cm*
Patients, n Event, n Follow-Up, patient-y Annual Risk, % (95% CI)
Aortic event without surgery
Aortic diameter (mm)
0–39 423 2 2353 0.09 (0.00–0.20)
40–44 219 1 995 0.10 (0.00–0.30)
45–49 157 2 675 0.30 (0.00–0.71)
50–54 54 1 75 1.33 (0.00–3.93)
55–59 14 1 12 8.14 (0.00–24.10)
Aortic event with surgery
Aortic diameter (mm)
0–39 423 7 2353 0.30 (0.08–0.52)
40–44 219 3 995 0.30 (0.00–0.64)
45–49 157 31 675 4.59 (2.98–6.21)
50–54 54 39 75 51.75 (35.51–68.00)
55–59 14 12 12 97.68 (42.41–100.00)
Annual Aortic Risk Depends Upon Aortic Size (732 patients, mean f/u 6.6 years) Jondeau G et al. Circulation 2012;125:226-232
Patients, n Event, n Follow-Up, patient-y Annual Risk, % (95% CI)
Aortic event without surgery
Aortic diameter (mm)
0–39 423 2 2353 0.09 (0.00–0.20)
40–44 219 1 995 0.10 (0.00–0.30)
45–49 157 2 675 0.30 (0.00–0.71)
50–54 54 1 75 1.33 (0.00–3.93)
55–59 14 1 12 8.14 (0.00–24.10)
Aortic event with surgery
Aortic diameter (mm)
0–39 423 7 2353 0.30 (0.08–0.52)
40–44 219 3 995 0.30 (0.00–0.64)
45–49 157 31 675 4.59 (2.98–6.21)
50–54 54 39 75 51.75 (35.51–68.00)
55–59 14 12 12 97.68 (42.41–100.00)
Annual Aortic Risk Depends Upon Aortic Size (732 patients, mean f/u 6.6 years) Jondeau G et al. Circulation 2012;125:226-232
Patients, n Event, n Follow-Up, patient-y Annual Risk, % (95% CI)
Aortic event without surgery
Aortic diameter (mm)
0–39 423 2 2353 0.09 (0.00–0.20)
40–44 219 1 995 0.10 (0.00–0.30)
45–49 157 2 675 0.30 (0.00–0.71)
50–54 54 1 75 1.33 (0.00–3.93)
55–59 14 1 12 8.14 (0.00–24.10)
Aortic event with surgery
Aortic diameter (mm)
0–39 423 7 2353 0.30 (0.08–0.52)
40–44 219 3 995 0.30 (0.00–0.64)
45–49 157 31 675 4.59 (2.98–6.21)
50–54 54 39 75 51.75 (35.51–68.00)
55–59 14 12 12 97.68 (42.41–100.00)
Annual Aortic Risk Depends Upon Aortic Size (732 patients, mean f/u 6.6 years) Jondeau G et al. Circulation 2012;125:226-232
Aortic Root Replacement in Marfan Syndrome
Special Considerations:
1. Family history of aortic dissection
2. Diffuse aortic enlargement
4. Rapid aortic growth rate (>5 mm/year)
5. Body surface area and gender
6. Requirement for mitral valve surgery
7. Aortic valve regurgitation 8. The patient’s desire to go forward now!
3. Prior type B aortic dissection
“Not All Aortic Aneurysms are Equal”
Underlying disease: LDS > MFS > BAV Family history of aortic dissection (size of aorta)
Rapid growth of aorta: 4 4.3 4.6 4.9 cm
4 4.1 4.1 4.2 cm
Body size/: 4.9 cm aorta in 6’5”, 235 lb (2 cm/m2) versus Gender 4.9 cm aorta in 5’9”, 125 lb (2.95 cm/m2)
Other predictors: ?biomarkers (TGF-β, microfibrils, fibrillin); aortic elasticity; wall stress /dynamic flow measurements; arterial tortuosity
18 patients (55%) underwent prophylactic aortic root replacement at a mean age of 25 + 14 yrs. 13 VSRR; 4 CVG; 1 homograft
LDS Adults (n=33)
TGFBR1 (n=16) TGFBR2 (n=17)
Aortic surgery 7 (44%) 16 (94%) Prophylactic aortic root replacement 6 (37.5%) 13 (71%)
Age at time of surgery (years)
33 + 19
21 + 9
Aortic size at time of prophylactic surgery (mm) 49 + 3 45 + 4
Descending TAA resection (non-dissection) 0 3 (18%)
Aortic dissection 2 (13%) 6 (35%)
Patient Mutation LDS FH Aortic size
Aortic dissection type, year and age Aortic Surgery
*SC TGFBR2 1 Yes (AD 26 yrs) 3.9 cm Type I (1997)
age 23
1997 CVG, hemiarch, ASD closure 1997 TAA graft 2005 brachiocephalic aneurysm section; aorta to RSC and R carotid bypass 2006 debranching and TEVAR of descending aortic patch and visceral pseudoaneurysms Died 2006 complications
*LS TGFBR2 1 No unknown Type 1 (2006) Age 21
2006 CVG 2007 arch/descending TAA resection (6 cm) 2007 Distal descending and abdominal
aortic replacement (5.6 cm)
MS TGFBR2 1 Yes (AD 53 yrs)
4.0 cm (after AD)
Type 1 (2012) (above root graft)
Age 34 [postpartum]
1996 VSRR 2013 replacement of ascending aorta; arch and 2/3 of descending aorta
KK TGFBR2 1 Yes
3.4 cm (3 mo before
AD
Type 1 (2013) (above root graft)
Age 22
2006 VSRR (Yacoub) 2012 AVR/Root (bioprosthetic) 2013 Ascending/arch to prox descending for acute rupture.
*CL TGFBR1 2 No 7.0 cm Type II (2011) age 18 2011 CVG
*AR TGFBR2 2 Yes unknown Type 1 (2001) Age 27
2001 supracoronary graft after acute AD 2005 CVG for root dilatation and AR 2009 TAA graft (extent II)
JM TGFBR2 2 No 4.3 cm Arch (2007) Age 33
Died 2007during surgical repair of aortic dissection (Prophylactic VSRR 2001)
JF TGFBR1 2 Yes (AD 42 yrs) 2.8 cm Type III (2010)
Age 39 [postpartum] 2010 Descending aortic graft 2010 TEVAR descending aorta for rupture. 2011 Ascending and arch graft
Aortic Dissection in Loeys-Dietz Syndrome
Patient Mutation LDS FH Aortic size
Aortic dissection type, year and age Aortic Surgery
*SC TGFBR2 1 Yes (AD 26 yrs) 3.9 cm Type I (1997)
age 23
1997 CVG, hemiarch, ASD closure 1997 TAA graft 2005 brachiocephalic aneurysm section; aorta to RSC and R carotid bypass 2006 debranching and TEVAR of descending aortic patch and visceral pseudoaneurysms Died 2006 complications
*LS TGFBR2 1 No unknown Type 1 (2006) Age 21
2006 CVG 2007 arch/descending TAA resection (6 cm) 2007 Distal descending and abdominal
aortic replacement (5.6 cm)
MS TGFBR2 1 Yes (AD 53 yrs)
4.0 cm (after AD)
Type 1 (2012) (above root graft)
Age 34 [postpartum]
1996 VSRR 2013 replacement of ascending aorta; arch and 2/3 of descending aorta
KK TGFBR2 1 Yes
3.4 cm (3 mo before
AD
Type 1 (2013) (above root graft)
Age 22
2006 VSRR (Yacoub) 2012 AVR/Root (bioprosthetic) 2013 Ascending/arch to prox descending for acute rupture.
*CL TGFBR1 2 No 7.0 cm Type II (2011) age 18 2011 CVG
*AR TGFBR2 2 Yes unknown Type 1 (2001) Age 27
2001 supracoronary graft after acute AD 2005 CVG for root dilatation and AR 2009 TAA graft (extent II)
JM TGFBR2 2 No 4.3 cm Arch (2007) Age 33
Died 2007during surgical repair of aortic dissection (Prophylactic VSRR 2001)
JF TGFBR1 2 Yes (AD 42 yrs) 2.8 cm Type III (2010)
Age 39 [postpartum] 2010 Descending aortic graft 2010 TEVAR descending aorta for rupture. 2011 Ascending and arch graft
Aortic Dissection in Loeys-Dietz Syndrome
Patient Mutation LDS FH Aortic size
Aortic dissection type, year and age Aortic Surgery
*SC TGFBR2 1 Yes (AD 26 yrs) 3.9 cm Type I (1997)
age 23
1997 CVG, hemiarch, ASD closure 1997 TAA graft 2005 brachiocephalic aneurysm section; aorta to RSC and R carotid bypass 2006 debranching and TEVAR of descending aortic patch and visceral pseudoaneurysms Died 2006 complications
*LS TGFBR2 1 No unknown Type 1 (2006) Age 21
2006 CVG 2007 arch/descending TAA resection (6 cm) 2007 Distal descending and abdominal
aortic replacement (5.6 cm)
MS TGFBR2 1 Yes (AD 53 yrs)
4.0 cm (after AD)
Type 1 (2012) (above root graft)
Age 34 [postpartum]
1996 VSRR 2013 replacement of ascending aorta; arch and 2/3 of descending aorta
KK TGFBR2 1 Yes
3.4 cm (3 mo before
AD
Type 1 (2013) (above root graft)
Age 22
2006 VSRR (Yacoub) 2012 AVR/Root (bioprosthetic) 2013 Ascending/arch to prox descending for acute rupture.
*CL TGFBR1 2 No 7.0 cm Type II (2011) age 18 2011 CVG
*AR TGFBR2 2 Yes unknown Type 1 (2001) Age 27
2001 supracoronary graft after acute AD 2005 CVG for root dilatation and AR 2009 TAA graft (extent II)
JM TGFBR2 2 No 4.3 cm Arch (2007) Age 33
Died 2007during surgical repair of aortic dissection (Prophylactic VSRR 2001)
JF TGFBR1 2 Yes (AD 42 yrs) 2.8 cm Type III (2010)
Age 39 [postpartum] 2010 Descending aortic graft 2010 TEVAR descending aorta for rupture. 2011 Ascending and arch graft
Aortic Dissection in Loeys-Dietz Syndrome
Patient Mutation LDS FH Aortic size
Aortic dissection type, year and age Aortic Surgery
*SC TGFBR2 1 Yes (AD 26 yrs) 3.9 cm Type I (1997)
age 23
1997 CVG, hemiarch, ASD closure 1997 TAA graft 2005 brachiocephalic aneurysm section; aorta to RSC and R carotid bypass 2006 debranching and TEVAR of descending aortic patch and visceral pseudoaneurysms Died 2006 complications
*LS TGFBR2 1 No unknown Type 1 (2006) Age 21
2006 CVG 2007 arch/descending TAA resection (6 cm) 2007 Distal descending and abdominal
aortic replacement (5.6 cm)
MS TGFBR2 1 Yes (AD 53 yrs)
4.0 cm (after AD)
Type 1 (2012) (above root graft)
Age 34 [postpartum]
1996 VSRR 2013 replacement of ascending aorta; arch and 2/3 of descending aorta
KK TGFBR2 1 Yes
3.4 cm (3 mo before
AD
Ascending (2013) (above root graft)
Age 22
2006 VSRR (Yacoub) 2012 AVR/Root (bioprosthetic) 2013 Ascending/arch to prox descending for acute rupture.
*CL TGFBR1 2 No 7.0 cm Type II (2011) age 18 2011 CVG
*AR TGFBR2 2 Yes unknown Type 1 (2001) Age 27
2001 supracoronary graft after acute AD 2005 CVG for root dilatation and AR 2009 TAA graft (extent II)
JM TGFBR2 2 No 4.3 cm Arch (2007) Age 33
Died 2007during surgical repair of aortic dissection (Prophylactic VSRR 2001)
JF TGFBR1 2 Yes (AD 42 yrs) 2.8 cm Type III (2010)
Age 39 [postpartum] 2010 Descending aortic graft 2010 TEVAR descending aorta for rupture. 2011 Ascending and arch graft
Aortic Dissection in Loeys-Dietz Syndrome
Patient Mutation LDS FH Aortic size
Aortic dissection type, year and age Aortic Surgery
*SC TGFBR2 1 Yes (AD 26 yrs) 3.9 cm Type I (1997)
age 23
1997 CVG, hemiarch, ASD closure 1997 TAA graft 2005 brachiocephalic aneurysm section; aorta to RSC and R carotid bypass 2006 debranching and TEVAR of descending aortic patch and visceral pseudoaneurysms Died 2006 complications
*LS TGFBR2 1 No unknown Type 1 (2006) Age 21
2006 CVG 2007 arch/descending TAA resection (6 cm) 2007 Distal descending and abdominal
aortic replacement (5.6 cm)
MS TGFBR2 1 Yes (AD 53 yrs)
4.0 cm (after AD)
Type 1 (2012) (above root graft)
Age 34 [postpartum]
1996 VSRR 2013 replacement of ascending aorta; arch and 2/3 of descending aorta
KK TGFBR2 1 Yes
3.4 cm (3 mo before
AD
Type 1 (2013) (above root graft)
Age 22
2006 VSRR (Yacoub) 2012 AVR/Root (bioprosthetic) 2013 Ascending/arch to prox descending for acute rupture.
*CL TGFBR1 2 No 7.0 cm Type II (2011) age 18 2011 CVG
*AR TGFBR2 2 Yes unknown Type 1 (2001) Age 27
2001 supracoronary graft after acute AD 2005 CVG for root dilatation and AR 2009 TAA graft (extent II)
JM TGFBR2 2 No 4.3 cm Arch (2007) Age 33
Died 2007during surgical repair of aortic dissection (Prophylactic VSRR 2001)
JF TGFBR1 2 Yes (AD 42 yrs) 2.8 cm Type III (2010)
Age 39 [postpartum] 2010 Descending aortic graft 2010 TEVAR descending aorta for rupture. 2011 Ascending and arch graft
Aortic Dissection in Loeys-Dietz Syndrome
Condition Aortic Size Threshold for Prophylactic Surgery*†
TAA with TAV 5.5 cm
TAA with BAV *5.5 cm (5.0 cm if +FH of AD or rapid growth)
Marfan Syndrome 5.0 cm 4.5 cm (if +FH of AD < 5cm)
Loeys-Dietz syndrome
~4.0 cm 4.2 cm (TEE)
4.4-4.6 cm (CT/MR) Children with severe CF features…
ACTA2/MYH11 ?4.5-5.0 cm SMAD3 Same as for LDS#
TGFB2 ?<5 cm Other FTAA/D ?5 cm (or as dictated by FH)
Turner syndrome ?2.5 cm/m2
*ratio aortic root area (cm2)/height (m) >10; rapid growth; FH; BSA; and gender considerations. #Roos-Hesselink et al. JACC 2012;60:397
†Aortic dissection reported at aortic size smaller than threshold in all conditions.
Thoracic Aortic Aneurysm Disease: What Disease is It? How to Treat?
1. It is important to make an accurate diagnosis of the underlying disease associated with thoracic aortic aneurysm. There is overlap in the phenotypes of genetically triggered aneurysm syndromes. Many cases have subtle features.
2. Multiple genes predispose to thoracic aortic aneurysms. One should screen 1st degree relatives for TAA disease. Mutation analysis may be very helpful in evaluating patients and families.
3. Phenotypic variation is not uncommon, even in families with the same mutation. There are likely multiple mechanisms influencing expression of mutations including modifiers, other genes, environmental and other factors.
Thoracic Aortic Aneurysm Disease: What Disease is it? How to Treat?
4. Education and awareness of thoracic aortic aneurysm syndromes impacts outcomes. Lifestyle modifications related to pregnancy, physical activity, and work are important, and prophylactic aortic surgery is lifesaving.
5. Advances in molecular, genetic, translational, and clinical research as well as in medical and surgical therapy hold great promise for those with TAA disease.
Thank you