Disclosure Statement
I DO NOT HAVE ANY RELEVANT
FINANCIAL RELATIONSHIPS WITH
ANY COMMERCIAL INTERESTS TO
DISCLOSE.
48th Southeast Pediatric Cardiology Society Conference
September 25 & 26, 2015
ADVANCES in AORTOPATHY
Walter H. Johnson, Jr., MD
UAB Department of Pediatrics
Division of Pediatric Cardiology
What is Aortopathy?
AORTOPATHY
Disease
Dilation
Dissection
AORTOPATHY
What’s more important?
Dilation?
Dissection?
AORTOPATHY
It depends!
AORTOPATHY
Dilation predicts
Dissection?
AORTOPATHY
It depends!
AORTOPATHY
Who has it and why does
it matter?
AORTOPATHY
CHD
GENETIC
AORTOPATHY
CHD
GENETIC
BAV
MFS
CT MALF
TS
etc
etc
AORTOPATHY
Why does it matter who
has it?
AORTOPATHY
DISSECTION RISK
DISSECTION RISK
HIGH RISK
LOW RISK
DISSECTION RISK
HIGH RISK
GENETIC
LOW RISK
CHD
HIGH
DISSECTION - RELATIVE RISK
Ehlers-Danlos (EDS) IV
Ehlers-Danlos (not Type IV)
Loeys-Dietz (LDS)
Fragile X
ACTA2
Incidental aneuploidy
MYH11
Conontruncal malformations
Marfan
Bicuspid aortic valve w/
dilation
Turner
Turner mosaics and males
Bicuspid aortic valve no
dilation
LOW
DISSECTION RISK
GENETIC
CHD
AORTOPATHY
How many patients are at
risk?
AORTOPATHY
Number at Risk
Bicuspid Aortic Valve
AORTOPATHY
Number at Risk
Bicuspid Aortic Valve
1 in 50 males
1 in 150 females
AORTOPATHY
Number at Risk
Turner Syndrome
AORTOPATHY
Number at Risk
Turner Syndrome
1 in 2500 female births
1 in 5000
AORTOPATHY
Number at Risk
Marfan Syndrome
AORTOPATHY
Number at Risk
Marfan Syndrome
1 in 3000 to 5000
ALABAMA
Pediatric Population
2015
TOTAL ~ 1.2 Million
(source - CDC)
AORTOPATHY
Number at Risk - Alabama
Marfan Syndrome
240-500
(birth to 19)
AORTOPATHY
Number at Risk - Alabama
Turner Syndrome
240
(birth to 19)
AORTOPATHY
Number at Risk - Alabama
Bicuspid Aortic Valve
12,000 males
4000 females
(birth to 19)
AORTOPATHY
Dilation predicts
Dissection?
Event rates and 95% confidence interval according to aortic diameter measured at the level of
the sinuses of Valsalva: (A) death or aortic dissection and (B) aortic surgery, death, or aortic
dissection.
Guillaume Jondeau et al. Aortic Event Rate in the Marfan Population- A Cohort Study. Circulation. 2012;125:226-232
Copyright © American Heart Association, Inc. All rights reserved.
TURNER SYNDROME
AORTIC DISSECTION TYPICALLY
OCCURS DESPITE STABLE AORTIC
SIZE
Venn diagram of 65 people with TS who had aortic dissection where signs of congenital heart
disease (CHD) or systemic hypertension (HTN) were explicitly considered.
Carlson M , Silberbach M J Med Genet 2007;44:745-749
©2007 by BMJ Publishing Group Ltd
ADULT AORTIC DISSECTION
ADULT AORTIC DISSECTION
Which patients dissect?
ADULT AORTIC DISSECTION
International Registry of
Aortic Dissection (IRAD)
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
YOUNGER (<40 Y) n = 68
OLDER (≥40 Y) n = 883
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
YOUNGER (<40 Y) n = 68
• MARFAN 50%
OLDER (≥40 Y) n = 883
• MARFAN 2%
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
YOUNGER (<40 Y) n = 68
• MARFAN 50%
• BAV 9%
OLDER (≥40 Y) n = 883
• MARFAN 2%
• BAV 1%
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
YOUNGER (<40 Y) n = 68
• MARFAN 50%
• BAV 9%
• HTN 34%
OLDER (≥40 Y) n = 883
• MARFAN 2%
• BAV 1%
• HTN 72%
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
YOUNGER (<40 Y) n = 68
• MARFAN 50%
• BAV 9%
• HTN 34%
• ATHEROSCLEROSIS 1%
OLDER (≥40 Y) n = 883
• MARFAN 2%
• BAV 1%
• HTN 72%
• ATHEROSCLEROSIS 30%
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
YOUNGER (<40 Y) n = 68
• MARFAN 50%
• BAV 9%
• HTN 34%
• ATHEROSCLEROSIS 1%
• PERIPARTUM 3%
OLDER (≥40 Y) n = 883
• MARFAN 2%
• BAV 1%
• HTN 72%
• ATHEROSCLEROSIS 30%
• PERIPARTUM 0%
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
What about the young
adults without Marfan,
BAV, or HTN?
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
Why did they dissect?
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
Almost all had aortic dilation
Figure 1. Distribution of aortic size at time of presentation with acute type A aortic dissection
(cm).
Linda A. Pape et al. Circulation. 2007;116:1120-1127
Copyright © American Heart Association, Inc. All rights reserved.
ADULT AORTIC DISSECTION
5 years - International Registry of Aortic Dissection (IRAD)
Aortic dilation alone is not a
perfect predictor
IDIOPATHIC AORTIC DISSECTION
Bicuspid aortic valve
occurs in ≥4% of
Marfan patients
IDIOPATHIC AORTIC DISSECTION
Bicuspid aortic valve
occurs in 50% of
Turner syndrome
patients
IDIOPATHIC AORTIC DISSECTION
We are good at
diagnosing bicuspid
aortic valve
IDIOPATHIC AORTIC DISSECTION
Maybe…we aren’t so
good at diagnosing
associated genetic
conditions
Pathophysiological Features of Bicuspid Aortopathy.
Verma S, Siu SC. N Engl J Med 2014;370:1920-1929
Figure 4. Complex hemodynamic stressors characterize the cardiac cycle in the proximal
aorta.
Martin G. Keane, and Reed E. Pyeritz Circulation.
2008;117:2802-2813
Copyright © American Heart Association, Inc. All rights reserved.
Figure 5. Interactions between combined hemodynamic stressors and underlying histologic
abnormalities result in a spiral of progressive degeneration and dilatation of aortic tissue.
Martin G. Keane, and Reed E. Pyeritz Circulation.
2008;117:2802-2813
Copyright © American Heart Association, Inc. All rights reserved.
From: The Role of Imaging in Aortic Dissection and Related Syndromes
J Am Coll Cardiol Img. 2014;7(4):406-424. doi:10.1016/j.jcmg.2013.10.015
Figure Legend:
Acute Aortic Syndromes
(A) Classic aortic dissection. (B) Aortic intramural hematoma. (C) Penetrating atherosclerotic aortic ulcer.
Copyright © The American College of Cardiology.
All rights reserved.
From: The Role of Imaging in Aortic Dissection and Related Syndromes
J Am Coll Cardiol Img. 2014;7(4):406-424. doi:10.1016/j.jcmg.2013.10.015
Copyright © The American College of Cardiology.
All rights reserved.
Subtypes and Complications of Aortic Dissection
Bonser, R. S. et al. J Am Coll Cardiol 2011;58:2455-2474
Copyright ©2011 American College of Cardiology Foundation. Restrictions may apply.
TGF-β Pathway in the Mature Aorta
Halushka HK. Cardiovasc Pathol. 2012 Jul-Aug;21(4):240-4.
Example - Clinical Genetic Testing
Aortopathy Panel - September 2015
ACTA2, CBS, COL3A1, COL5A1, COL5A2,
FBN1, FBN2, FLNA*, MED12*,
MYH11, SKI*, SLC2A10, SMAD3, TGFB2*,
TGFBR1, TGFBR2
Clinical Genetic Testing
Unlike school tests,
these tests only help
you if you flunk them.
Example - Clinical Genetic Evaluation
Ghent Criteria - Marfan Syndrome
In the absence of family history:
(1) Ao (Z ≥ 2) AND EL = MFS*
(2) Ao (Z ≥ 2) AND FBN1 = MFS
(3) Ao (Z ≥ 2) AND Syst (≥7pts) = MFS*
(4) EL AND FBN1 with known Ao = MFS
Loeys B et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet
2010 47: 476-485
What is NORMAL?
From: 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management
of Patients With Thoracic Aortic Disease
J Am Coll Cardiol. 2010;55(14):e27-e129. doi:10.1016/j.jacc.2010.02.015
Normal diameter and upper limit of ascending and descending aorta related to age.
Copyright © The American College of Cardiology.
All rights reserved.
Relationship between untransformed ascending aorta diameter and body surface area
(BSA).
A E Warren et al. Heart 2006;92:1496-1500
Copyright © BMJ Publishing Group Ltd & British Cardiovascular Society. All rights reserved.
Figure 1
Stratification of Pediatric Patients with Idiopathic Thoracic Aortic Aneurysm
Landis BJ et al
The Journal of Pediatrics 2015 167, 131-137.e5DOI: (10.1016/j.jpeds.2015.02.042)
Copyright © 2015 Elsevier Inc. Terms and Conditions
MEDICATION
MEDICATION
Why?
MEDICATION
•
•
•
•
•
Low risk
Might be of benefit
Do something vs nothing
Make some feel better
"Standard of Care"??
MEDICATION
• Beta-blockers
• ARB’s
• Others (ACEI; Ca Channel
blockers; others)
MEDICATION
• ATENOLOL
• LOSARTAN
Lacro RV et al. N Engl J Med 2014;371:2061-2071
Mean and individual slopes of aortic root dilatation in the population receiving placebo (top)
or Losartan (bottom).
Olivier Milleron et al. Eur Heart J 2015;eurheartj.ehv151
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2015. For permissions please email: journals.permissions@oup.com.
MEDICATION
•
•
•
•
Not a cure
Won't prevent dissection
Won't prevent dilation
Won't work for all patients
MEDICATION
• Might benefit some by
slowing dilation rate
• Low Risk
MEDICATION
• ALL are OFF-LABEL
Pathophysiology of Marfan syndrome and possible sites for drug treatment.
A Williams et al. Heart 2008;94:414-421
Copyright © BMJ Publishing Group Ltd & British Cardiovascular Society. All rights reserved.
SURGERY
SURGERY
• Indications
• Based on Dissection Risk
• Bigger Aorta ≈ Bigger Risk
• Rapid Dilation
SURGERY
• Indications
• Based on Dissection Risk
• Bigger Aorta ≈ Bigger Risk
• Rapid Dilation
• Dissection
SURGERY
• Indications
• Based on Dissection Risk
• LDS > MFS > BAV
SURGERY
• Indications – Marfan
• SIZE
• Adult SOV >50 mm
• (>45 mm if fam hx dissection)
• RATE
• > 5 mm/year
Diameter of the Aneurysm in 524 Adult Patients with Marfan's Syndrome,
According to the Presence of Aortic Dissection
Gott V et al. N Engl J Med 1999;340:1307-1313
SURGERY
• Aortic Root Replacement
• Valve Replacement
• Valve-Sparing
• Root Remodeling
• External
Kirklin JK et al. Novel Technique of Valve-Sparing Aortic Root Replacement in Two
Children Younger Than 3 Years of Age. Ann Thorac Surg 2012;94:299 –301
Fig. 1. Imaging data retrieved from the CMR study (A) is used to produce an exact model of each patient's aorta by using computer
aided design and rapid prototyping (B) and then a bespoke porous, soft and pliable mesh is produced that is ready for implantation...
Cemil Izgi, Evangelia Nyktari, Francisco Alpendurada, Annina Studer Bruengger, John Pepper, Tom Treasure, Raad Mohiaddin.
Effect of personalized external aortic root support on aortic root motion and distension in Marfan syndrome patients.
International Journal of Cardiology, Volume 197, 2015, 154–160. http://dx.doi.org/10.1016/j.ijcard.2015.06.015
SURGERY
•
•
•
•
Not a cure
Won't prevent dissection
Won't prevent dilation
Increases some risks
SURGERY
•
•
•
•
Not a cure
Won't prevent dissection
Won't prevent dilation
Increases some risks
• Dissection
• Dilation
• Valve Dysfunction
ENDOVASCULAR
ENDOVASCULAR
Cambria RP. TEVAR for Descending
Thoracic Aortic Aneurysms
AORTOPATHY CLINIC
• Education
• Medication Limitations
• Dissection Education
• Emergent Care
