Update on the Diagnosis & Management of Acute Aortic Dissection

(1)

Update on the Diagnosis &

Management of Acute Aortic Dissection

Kim A. Eagle, MD

Director

University of Michigan

Cardiovascular Center

(2)

Kim A. Eagle, MD, FACC

Director

University of Michigan

Cardiovascular Center

Grants:

Hewlett Foundation, Mardigian

Foundation, Varbedian Fund, GORE

(3)

“

Acute Aortic Syndromes

”

•

Classic Aortic

Dissection

•

Intramural

Hematoma

•

Penetrating

Aortic Ulcer

Aortic

Dissection

IMH

PAU

(4)

“Atypical" Aortic Dissection

(Intramural Hematoma)

“Atypical" Aortic Dissection

(Intramural Hematoma)

TL

FL

Typical = Dissection flap and false lumen

(5)

IRAD Classification System

Type A Dissection

IRAD Investigators

56

49

42

35

28

21

14

7

0

Days From Symptom Onset

Probability of Sur

vival

0.0

0.2

0.8

1.0

Surgical Management

Medical Management

Log Rank p<0.001 (Between Managements) 8-21 Days (Subacute) >21 Days (Chronic) 2-7 Days (Acute) 0-24 Hours (Hyperacute)

0.4

0.6

(6)

IRAD Classification System

Type B Dissection

56

49

42

35

28

21

14

7

0

Days From Symptom Onset

Probability of Sur

vival

0.7

0.8

0.9

1.0

Surgical Management

Medical Management

Endovascular Management

Log Rank p<0.001 (Between Managements) 8-21 Days (Subacute) >21 Days (Chronic) 2-7 Days (Acute) 0-24 Hours (Hyperacute) IRAD Investigators

(7)

Variable

All

Type A Type B p-value

(n=3037)

(n=1924)

(n=1113)

Age (yrs)

61.9

61.3

63.0

0.003

Male

67.1%

67.2%

67.1%

NS

HTN

75.2%

72.0%

80.7%

<0.001

Marfan

4.3%

4.5%

3.8%

NS

Prior Heart

16.9%

15.3%

19.8%

0.002

Surgery

Iatrogenic

3.3%

3.8%

2.6%

0.09

Demographics and Past History

(8)

Genetic

Syndrome

Common

Clinical

Features

Genetic

Defect

Diagnostic

Test

Marfan

Syndrome

Skeletal featuresEctopic lentleSkeletal featuresEctopic lentle FBN1mutations*FBN1mutations*

Ghent diagnostic Ghent diagnostic Criteria, DNA for Criteria, DNA for sequencing

sequencing

Loeys

-

Dietz

Syndrome

Bifid uvula or cleft Bifid uvula or cleft palate palate Arterial tortuosity Arterial tortuosity Hypertelorism Hypertelorism TGFBR2 TGFBR2 oror TGFBR1 TGFBR1 mutations mutations DNA for DNA for sequencing sequencing

Ehlers

-

Danios

Syndrome

Thin, translucent Thin, translucent skin GI rupture skin GI rupture Rupture of gravid Rupture of gravid uterus uterus Rupture of medium Rupture of medium to large arteries to large arteries COL3A1 COL3A1 mutations mutations

DNA for sequencing DNA for sequencing Dermal fibroblasts Dermal fibroblasts for analysis of type for analysis of type 3 collagen 3 collagen

Turner

Syndrome

Short stature Short stature Primary amenorhea Primary amenorhea BAV BAV Aortic coarctation Aortic coarctation 45 X 45 X karyotype

karyotype Cells for karyotype analysisCells for karyotype analysis

Genetic Disorders:

Thoracic Aortic Disease

(9)

Genetics of Familial Thoracic

(n = 454 Families)

Defective Gene

Leading to

Familial

TAAD

Frequency in

Familial TAAD

Associated

Clinical

Features

Comments on

Aortic Disease

Management

TGFBR2

mutation

(R460)

4%

Thin translucent Thin translucent skin skin Arterial tortuosity Arterial tortuosity is more common is more common in older in older individuals individuals Aneurysms of Aneurysms of arteries arteries Multiple aortic Multiple aortic dissections dissections documented at documented at aortic diameters aortic diameters <5.0cm <5.0cm

MYH11

mutations

1%

PDAPDA

Patient with Patient with document document dissection at dissection at 4.5cm 4.5cm

ACTA2

mutations

14%

Livedo reticularisIris flocculiLivedo reticularisIris flocculi

2 of 13 patients 2 of 13 patients with documented with documented dissections dissections <5.0cm <5.0cm

(10)

TAD Guidelines: Genetic Conditions

Condition

Marfan

Syndrome

Recommendation

• Echo at Dx and 6

months

• Echo annually if stable

• Echo more often if Ao.

Diam. increasing or

>4.5cm

• Prophyllactic surgery at

4.5-5.0cm

• Prophyllactic surgery in

women planning

pregnancy at 4.0cm

Evid. Level

Ι

ΙΙa

(11)

TAD Guidelines: Genetic Conditions

Condition

Loeys-Dietz

or

TGFBR 1 or 2

Turner

Syndrome

Loeys-Dietz

or

TGFBR 1 or 2

Recommendation

• Complete aortic

imaging at Dx and

6 months

• Annual complete aortic

MRI: Brain to pelvis

• Heart and aortic

imaging at Dx

• If abnormal

→

annual

• If normal

→

aortic

imaging 5-10 years

• Aortic repair:

4.2cm by TEE

4.4-4.6cm by CT

Evid. Level

Ι

ΙΙ

ΙΙa

(12)

Condition

BiCuspid

Aortic

Valve

Documented

genetic aortic

conditions

(FBNI, TGFBR

1 & 2, COL3AI,

ACTA2, MYH

II)

Recommendation

• Aortic root/Asc. aorta

imaged

• Aortic imaging of

1

st

degree relatives

• First degree relatives

undergo counseling

at testing;

• Genetic positives

undergo aortic

imaging

Evid. Level

Ι

(13)

p-value

<0.001

0.06

<0.001

0.004

<0.001

IRAD

Presenting Symptoms

Variable

•

Pain

Abrupt

Abdominal

Sharp

Tearing

•

Syncope

All

94.0%

84.0%

71.9%

53.1%

31.2%

62.8%

47.1%

12.6%

Type A

92.6%

82.9%

78.0%

42.8%

25.5%

58.4%

44.0%

18.3%

Type B

96.5%

85.7%

61.1%

70.5%

40.8%

69.4%

52.0%

2.9%

IRAD Investigators

(n=2807)

(14)

IRAD

Physical Exam

(n=2820)

Variable

High BP

Low BP

Shock/Tamponade

Murmur AI

Pulse Deficit

Stroke

All

43.3%

11.4%

8.0%

27.6%

25.7%

6.5%

Type A

30.3%

16.0%

12.0%

38.3%

30.5%

9.1%

Type B

65.3%

3.5%

1.3%

10.7%

18.1%

2.2%

p-value

<0.001

IRAD Investigators

(15)

Variable

•

CXR

Normal

Wide Mediast.

or Aorta

PL. Effusion

•

EKG

Normal

NSST-T ’s

Ischemia

New MI

IRAD

EKG & CXR

(n=2353)

All

22.4%

67.6%

14.4%

32.2%

40.7%

14.3%

5.5%

Type A

20.2%

69.5%

12.5%

29.9%

41.2%

17.1%

7.4%

Type B

25.9%

64.5%

17.3%

36.2%

39.8%

9.6%

2.1%

p-value

0.001

0.012

0.002

0.001

NS

<0.001

IRAD Investigators

(16)

D

-

Dimer Levels in Aortic Dissection

Suzuki T, et al. Circulation 2009;119:2702-07.

0 1000 2000 3000 4000 5000

D-Dimer (ng/ml)

AD+(A) n=19 AD+(B) n=4 MI n=9 Angina n=14 PE n=2

Time after onset (0-6h)

AD+(A) n=26 AD+(B) n=7 MI n=14 Angina n=5 PE

Time after onset (6-12h)

AD+(A) n=19 AD+(B) n=12 MI n=23 Angina n=18 PE n=3

(17)

Sensitivity of the First Imaging Study to

Detect AoD and Intramural Hematoma

IRAD Investigators

85.5%

97.3%

96.9%

87.3%

559 559 654 654 1880 1880 1933 1933 31₃₂31₃₂ ₆₂₆₂ 71 71

(n=2690)

(18)

Who are You Measuring?

Aortic Diameter at Sinuses of Valsalva by

Gender (Adjusted for BSA)

NS p<0.001 p<0.001 p<0.001 p<0.001 p<0.001 p=0.002

Men Women

Diameter (cm)

(19)

Proportion of U.S. Citizens with

Dilated Ascending Aortas

Proportion of U.S. Citizens with

Dilated Ascending Aortas

4.2 - 4.4cm

3,800,000

+

4.5 – 4.9cm

1,600,000

+

≥

5.0cm

200,000

+

20% caused by genetic condition.

(20)

Aortic Aneurysms:

Yearly Risk of Complications

Scientific American, August: 2005.

Average Yearly Rate of

Complications (%)

Rupture

Dissection

Rupture or

Dissection

Diameter of Diameter of Aneurysm (cm) Aneurysm (cm) 4.0 to 4.9 4.0 to 4.9 5.0 to 5.9 5.0 to 5.9 6.0 or greater 6.0 or greater

(21)

Maximum Aorta Diameter:

Type A Dissection

Pape et al. AHA 2005.

(22)

Descending Aortic Diameter

≥

6.0cm: A

Poor Predictor of Type B Aortic Dissection

Count

Trimarchi S, et al. J Am Coll Cardiol 2009;53: A452.

Descending Diameter

(23)

• Medical Therapy for all, for life

• Surgery if possible….esp A

1

>A

2

>A

3

• Consider fenestration if surgery not

possible, especially if malperfusion

occurs

Type A Dissection

(24)

In

-

hospital Survival

in TA

-

AAD

Sinha S, presented ACC 2011.

Follow-up Survival in

TA-AAD

(25)

• Uncomplicated - No false lumen:

Medical

• Uncomplicated - False channel

+/- aneurysm - consider stent

• Complicated - stent +/- surgery

Type B Dissection

Nienaber CA, et al. Circulation 2003;108:628-635.

(26)

Comparison of Medical Therapy to

Endovascular Treatment in Type B

Dissection:

Long Term Follow-Up

Comparison of Medical Therapy to

Endovascular Treatment in Type B

Dissection:

Long Term Follow-Up

Fattori R, et al. Circulation 2010.

Endovascular

Year of Follow-up

0

1

2

3

4

5

1.0

0

0.2

0.4

0.6

0.8

Survival

log rank p=0.05

Medical

(n=89)

(n=320)

(27)

• Evidence of leakage or subacute rupture

• Extensive false channel despite excellent

medical Rx

• Extensive aneurysm

• Progressive morbidity despite medical Rx

Stent Graft Therapy

Indications in Acute Dissection

Nienaber CA, et al. Circulation 2003;108:628-635.

(28)

1. Beta-blockers

2. Ca++ blockers

3. ACE/ARB

4. Statins

Follow

(29)

Medical Management

CITATION

STUDY DESIGN

RESULTS

Genoni et al. Eur J

CardioThorac

Surg. 2001;

5:606-10.

Retrospective: 78/130

pts with chronic

dissection on medical

therapy only

Dissection Related Surgery

51/71 B-blocker

→

10 (19%)

20/71 other

→

9 (45%)

Aortic Expansion

BB 6/51 (12%)

Other 8/20 (40%)

Shores, et al.

NEJM

1994;330:1335.

Randomized Trial in

Aortic Root Disease

(propranolol 212±68 mg)

Aortic Dilation Rate

Propranolol 0.023 cm/yr

Not on BB 0.084 cm/yr

Ladoceur et al.

Am J Cardiol

2007; 99:406.

Retrospective; Ao

Dilation in children with

Marfan Syndrome

(30)

Beta Adrenergic Blockade Slows

Aorta Growth in Marfan

’

s

Shores, J. NEJM 1994; 330:1335-1341.

Randomized trial of propranolol in 70 adolescent and adult

(31)

Beta

-

Blockers Lower Risk

in Ehler

-

Danos

Kaplan-Meier curves of event-free survival in 53 patients with vascular Ehlers-Danlos Primary endpoint (A). Primary and secondary endpoints (B).

(32)

Medical Management: ACE & ARBs

CITATION

STUDY DESIGN

RESULTS

Hackam et al.

Lancet

2006;368:659.

Retrospective, Case

control, Population

Based

ACE inhibition prior to

admission:

Decr. likelihood of rupture

Aneurysm OR 0.82

(0.74-0.90)

Mochizuki et al.

Lancet

2007; 369:

1431.

Randomized with HTN,

CAD or CHF to

Valsartan (40-160mg)

or other.

Valsartan decreased:

Composite CV outcome- OR

0.61 (0.47-0.79)

Aortic Dissection- OR 0.18

(0.04-0.88)

(33)

Jikei Heart Study

Mochizuki S, et al. Lancet2007;369:1431-39.

Non-ARB

All Patients Valsartan Group Treatment Group

Calcium-channel blocker 2052 (67%)

1041 (68%)

1011 (66%)

ACE inhibitor

1073 (35%)

548 (36%)

525 (34%)

Blocker

988 (32%)

486 (32%)

502 (33%)

Blocker

167 (5%)

74 (5%)

93 (6%)

Thiazide

68 (2%)

29 (2%)

39 (3%)

Antialdosterone agent

116 (4%)

52 (3%)

64 (4%)

Other diuretics

243 (8%)

117 (8%)

126 (8%)

Statin

951 (31%)

461 (30%)

490 (32%)

Fibrate

79 (3%)

42 (3%)

37 (2%)

Dissection

12 (0.7%)

2 (0.1%)

10 (0.6%)

α

β

(34)

Long

-

Term

• B-Blockers: HR <60BPM

• Control Blood Pressure: <120/80

-Prefer ARB’s or ACE’s

• Statins for atherosclerosis

• “Watch” for aneurysm formation: 1, 3,

6, 12 months to start

• Educate the patient: a lifelong

disease; sx, activity, meds, f/up

(35)

Where is the Future?

Clinical Data

Treatments

Family History

Demographics

Environmental

Imaging

Gene Expression Profiles

Genomic Data

SNP

’

s

Genome

-

scale sequence

Metabolic Data

Proteomic Data

?

Predictions:

Risk

Individualized Prognosis & Diagnosis

Drug Response

Environment (e.g. Diet) Response

Patterns

Integration

Models