Chapter 140 - aneurysms caused by connective tissue abnormalities Flashcards
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
Connective tissue disease define
1) genetic disease 2) primary target is collagen or elastin
Structural elements of blood vessels
TABLE 140.1
First description of Marfan
1896 Antonin-Bernard Marfan 1943 first full description
Marfan epidemiology
1) 2-3/10000 2) autosomal dominant 3) 25% sporadic de novo mutation 4) no gender predisposition
Cause of death in marfan
1) aortic rupture 2) aortic dissection 3) valvular disease
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
Ghent criteria for Marfan 2010 revised
BOX 140.1
Criteria for causal FBN1 mutation
BOX 140.2
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
Shprintzen-Goldberg syndrome
1) craniosynostosis 2) facial hypoplasia 3) anterior chest deformity 4) arachnodactyly 5) aortic root dilatation 6) developmental delay FBN1 point mutation
Locus of marfan disease genetic chromosome
15q21.1
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
Congenital contractural arachnodactyly
1) NO ocular and cardiovascular manifestation FBN2 gene mutation
Differential for Marfan
1) MASS phenotype 2) Shprintzen-Goldberg syndrome 3) Homocystinuria 4) Congenital contractural arachnodactyly 5) Loeys Dietz
Marfan manifestation
1) ocular 2) skeletal 3) cardiovascular
When does aortic root dilatation begin in Marfan
In utero
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
Z score define
Nomogram defining the number of SD of the patient aortic root diameter from mean diameter of population
Prevention of aortic root disease in Marfan
Avoid burst exertions
Medical treatment of Marfan aortic root growth
1) beta-blocker 2) losartan (also reduces TBAD)
Target HR in Marfan
70 beats/min at rest 100 beats/min with exercise
Beta blocker effect weaker when these conditions occur
1) heavier patient 2) diameter > 4cm already
Losartan regimen in Marfan
maximum 2mg/kg up to 100 mg
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
