Chapter 140 - aneurysms caused by connective tissue abnormalities Flashcards by Gary Yang

Connective tissue disease that lead to aneurysms

1) Marfan syndrome 2) Vascular type of Ehlers-Danlos (EDS IV or VEDS) 3) Loeys-Dietz 4) familial thoracic aortic aneurysm and dissection

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Connective tissue disease define

1) genetic disease 2) primary target is collagen or elastin

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Structural elements of blood vessels

TABLE 140.1

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First description of Marfan

1896 Antonin-Bernard Marfan 1943 first full description

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Marfan epidemiology

1) 2-3/10000 2) autosomal dominant 3) 25% sporadic de novo mutation 4) no gender predisposition

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Cause of death in marfan

1) aortic rupture 2) aortic dissection 3) valvular disease

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Pathogenesis of Marfan

1) Fibrillin-1 (FBN1) mutation 2) failure to maintain normal elastic fibers 3) matrix metalloproteinase 2 and 9 4) inflammation and calcification weakens elastic fibers ALSO 2) TGF beta complex cannot bind microfibril 3) excessive TGF beta signalling

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Ghent criteria for Marfan 2010 revised

BOX 140.1

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Criteria for causal FBN1 mutation

BOX 140.2

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MASS phenotype

1) Mitral valve prolapse 2) myopia 3) mild aortic root dilatation 4) striae 5) mild skeletal changes FBN1 mutation created premature termination codons

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Shprintzen-Goldberg syndrome

1) craniosynostosis 2) facial hypoplasia 3) anterior chest deformity 4) arachnodactyly 5) aortic root dilatation 6) developmental delay FBN1 point mutation

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Locus of marfan disease genetic chromosome

15q21.1

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Homocystinuria

Deficiency of cystathionine beta-synthase 1) long bone overgrowth 2) ectopia lentis 3) NO aortic enlargement 4) mental retardation 5) thromboembolism 6) coronary disease 7) elevated homocysteine autosomal recessive

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Congenital contractural arachnodactyly

1) NO ocular and cardiovascular manifestation FBN2 gene mutation

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Differential for Marfan

1) MASS phenotype 2) Shprintzen-Goldberg syndrome 3) Homocystinuria 4) Congenital contractural arachnodactyly 5) Loeys Dietz

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Marfan manifestation

1) ocular 2) skeletal 3) cardiovascular

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When does aortic root dilatation begin in Marfan

In utero

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Indication to repair aortic root in Marfan

1) children growth > 1cm/yr 2) Z score > 2-3 SD 3) adult > 5cm 4) family history of dissection

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Z score define

Nomogram defining the number of SD of the patient aortic root diameter from mean diameter of population

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Prevention of aortic root disease in Marfan

Avoid burst exertions

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Medical treatment of Marfan aortic root growth

1) beta-blocker 2) losartan (also reduces TBAD)

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Target HR in Marfan

70 beats/min at rest 100 beats/min with exercise

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Beta blocker effect weaker when these conditions occur

1) heavier patient 2) diameter > 4cm already

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Losartan regimen in Marfan

maximum 2mg/kg up to 100 mg

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Indication for surgical repair in Marfan

1) aortic root \> 5cm 2) arch and descending \> 5.5-6 cm 3) symptomatic

First thoracoabdominal aortic repair in marfan

Crawford 1980

Long term mortality and spinal cord injury in marfan vs atherosclerotic disease

Lower mortality and lower risk of spinal ischemia in Marfan's

Key long term complicadtion of open aortic repair in Marfan

Visceral patch degeneration into aneurysm Repair when 6cm or larger

SINE stands for what in terms of endo aortic repair

Stent-graft induced new entry tears

Rate of new dissection in endo repair of marfan aorta

25% mortality is 42% after treatment failure

Subtypes of Ehlers-Danlos

TABLE 140.2

Pathogenesis of type 4 EDS

defective type 3 procollagen (COL3A1 gene)

Epiedmiology of EDS 4 and genetics

1) 1 in 50000-90000 2) autosomal dominant 3) 50% are de novo 4) each family carries a unique mutation in COL3A1 gene

EDS4 life expectancy

48 (6-73) years

Natural history of EDS4

1) Age 20 25% had complication 2) Age 40, 89% major complication vascular and GI and reproductive

Cause of death in EDS4

1) vascular rupture 60% 2) CNS hemorrhage 7% 3) unspecified bleed 12% 4) organ rupture 10% 5) intestinal rupture 8%

COL3A1 gene function

1) Codes proal(III) = procollagen molecule 2) 3 procollagen molecule form alpha chain triple helix 3) mutation prevents triple helix and are degraded before being secreted extracellularly

Diagnostic criteria for EDS4

MAJOR 1) thin translucent skin 2) arterial/intestinal/uterine fragility or rupture 3) extensive bruising 4) characteristic facial appearance MINOR 1) acrogeria (taut thin skin) 2) hypermobility of small joints 3) tendon and muscle rupture 4) talipes equinovarus (clubfoot) 5) early onset varicose veins 6) AV carotid-cavernous sinus fistula 7) pneumothorax/pneumohemothorax 8) gingival recession 9) positive family history, sudden death in one or more close relatives

Testing for EDS4

Direct molecular genetic analysis of COL3A1 gene from serum sample

Most often type of dissections in EDS4

Medium sized vessels unlike MFS where it's mostly in aorta

Differentiating between EDS4 and LDS in terms of arterial tortuosity syndrome

Surgery well tolerated in LDS but not in EDS4

Anesthesia considerations in treating EDS4

1) cross match adequate blood 2) avoid IM injections 3) ensure adequate peripheral access 4) avoid art line and CVC 5) gentle intubation maneuvers

Rate of true aneurysms in EDS4

14%

Complication rate and mortality in EDS4 from access site

67% complication, 12% mortality

Suture techniques for bleeds in EDS4

1) vessel ligation with umbilical tape when possible 2) pledgetted tensionless reconstruction 3) circumferentially reinforced

Signs that EDS4 patient has inoperable tissue fragility

1) identified \< 20 years old 2) multiple asymptomatic dissection/aneurysms noted

Nonvascular complications in EDS4

GI perforation 25% - sigmoid most common - ostomy first

Rate of recurrent bowel perf in EDS4

17% in 26 years

Non-surgical treatment of EDS4

1) celiprolol (controversial) 2) BP control 3) lifestyle modifications 4) Factor VII transfusion

Hopkins 1994-2009 recommendation in EDS4

1) liberal use of adjunctive technique to reduce operative trauma 2) padded surgical clamps 3) permissive hypotension (SBP 70-80) during clamp and anastamosis testing

Unique iliac aneurysms in EDS4

1) spares aortic bifurcation 2) bell-bottom CIA

Role of endo in EDS4

1) generally do not use 2) access site problem needs open repair 3) embolization of aortic branch and medium vessel and carotid-cavernous sinus fistula can work

Maternal mortality in 2 weeks post partum in EDS4

15%

Loeys Dietz Syndrome classic symptoms

1) aortic syndrome with aneurysm and vascular tortuosity 98% 2) craniaofacial abn (bifid uvula, cleft palate) 90% 3) hypertelorism (90%) 4) craniosynostosis (premature closure of skull) 48% 5) malar hypoplasia (flat midface) 60% 6) blue sclerae 40%

Gene mutation in LDS

1) Heterozygous mutation 2) TGF beta receptor 1 and 2 (TGFBR1, TGFBR2) 3) SMAD3 4) TGF-B2 receptor

Subtypes of LDS

TYPE 1: severe craniofacial and aortic aneurysm TYPE 2: less severe craniofacial (bifid uvula or high palate) and aneurysm TYPE 3: aortic aneurysm with early-onset osteoarthritis TYPE 4: aortic aneurysm, cerebral aneurysm, arterial tortuosity

Cardinal manifestation of LDS aorta

1) aortic root dilatation 2) rupture and dissect at lower diameters than MFS and EDS4

Systemic features in LDS

BOX 140.4

Onset of disease in different LDS subtypes

More craniofacial abn = more aggressive aortic path = earlier surgery TYPE 1: first surgery 16.9 years old; death 22.6 years old TYPE 2: first surgery 26.9 years old; death 31.8 years old TYPE 3 and 4 later onset

Difference in eye manifestation of LDS from MFS

Lens dislocation (ectopia lentis) only in MFS

Size and growth of aortic aneurysm indicating repair in LDS

4 cm growth \> 0.5 cm/year

Medical treatment of LDS

beta blocker, losartan (for TGF beta activity) and lifestyle modification no clear evidence

How to avoid kinking in visceral aortic repair to the branches

360 degrees wrapping of the branch graft minimize patch inclusion from the vessel wall to prevent patch degeneration and patch aneurysm

Familial thoracic aortic aneurysm and dissection definition

1) not MFS, EDS4, LDS 2) 11-19% of all still have first degree relative 3) audosomal dominant with variable penetrance and expression

TAAD1 locus 5q13-14 key points

1) autosomal dominant 2) women less affected 3) ascending aorta involvement

Pathogenesis of familial TAAD

1) medial degeneration 2) disarray of SMC and accumulation of proteoglycan

ACTA2 mutation alpha-actin mutation

1) 14% of familial TAAD 2) low penetrance and does not change with age (different from other TAAD types)

Familial TAAD age onset of aneurysm vs sporadic aneurysms

58.2 years vs 65.7 years otherwise normal

Aneurysm frequency and types in familial TAAD

1) thoracic 66% 2) AAA 25% 3) cerebral 8-10%

Ascending and descending aorta in familial TAAD, aneurysm vs dissection frequency

Ascending aneurysm 82%; dissection 18% Descending aneurysm, dissection 50/50%

Size for repair of familial TAAD aneurysms

Same as others 6 thoracic 5.5 abdominal growth is faster 0.21 vs 0.16cm/yr