Presentazione di PowerPoint - Società Italiana di ... · defined above) = MFS *without discriminating features of Loeys-Dietz syndrome, vascular EDS or Shprintzen-Goldberg syndrome

San Raffaele Scientific Institute - Vascular Surgery - Università “Vita-Salute”, Milano

Germano Melissano“Vita-Salute” - San Raffaele University – Milano (Italy)

[email protected]

Update sulla patologia aneurismatica nel Marfan

San Raffaele Scientific Institute - Vascular Surgery - Università “Vita-Salute”, Milano 2

Disclosures

No relevant disclosures


Clinical presentation of TAA or TAD

• Early onset

• Lack of typical risk factors

• Runs in the family

• (Syndromic features)

MFS / CTD


TAA or TAD may have a genetic basisMFS is just the tip of the iceberg

John A. Elefteriades


Syndromic TAA• Marfan syndrome FBN1

• Ehlers-Danlos syndrome

– Vascular COL3A1

– Kyphoscoliotic PLOD1

– Valvular COL1A2

– EDS/OI overlap COL1A1

– Periventricular heterotopia FLNA

• Shprintzen-Goldberg syndrome SKI

• Cutis laxa FBLN4, ELN

• Arterial tortuosity syndrome SLC2A10

• Loeys-Dietz syndrome I/II TGFBR1/2

• Aneurysm/osteoarthritis – LDS IIISMAD3

• Loeys-Dietz syndrome IV TGFB2


Diagnosis of MFS

Quite obvious when its key phenotypic characteristics are present,

quite challenging if not…

Variable phenotype: in many cases they don’t look like the archetypal MFS


Marfan syndrome (MFS)

Deficiency of FIBRILLIN-1 (FBN1)

Clinical diagnosis based on the revised nosology

Bart Loeys et al. J Med Genet, 2010


The revised nosology: basic rules

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:(5) EL + FH of MFS (as defined above) = MFS(6) Syst (≥7 pts) + FH of MFS (as defined above) = MFS(7) Ao (Z≥2 in adults, Z≥3 in children) + FH of MFS (as defined above) = MFS

*without discriminating features of Loeys-Dietz syndrome, vascular EDS or Shprintzen-Goldberg syndrome



Revised nosology: systemic score

2 points

3 points+



1 point

Revised nosology: systemic score



Wrist AND thumb sign – 3 (Wrist OR thumb sign – 1)

Pectus carinatum deformity – 2 (pectus excavatum or chest asymmetry - 1)

Hindfoot deformity – 2 (plain pes planus – 1)

Protrusio acetabuli – 2

Pneumothorax – 2

Dural ectasia – 2

Reduced US/LS AND increased arm/height AND no severe scoliosis – 1

Scoliosis or thoracolumbar kyphosis – 1

Reduced elbow extension – 1

Facial features (3/5) – 1

(dolichocephaly, enophtalmos, downslanting palpebral fissures, malar

hypoplasia, retrognathia)

Skin striae – 1

Myopia > 3 diopters - 1

Mitral valve prolapse (all types) – 1

Systemic score ≥ 7 = MFS


CTD = problem in extra cellular matrix (ECM)

• ECM: Important proteins (collagen, fibrillin, elastin etc.) = biomechanicalproperties…But also …

• Regulates cytokines, TGFBeta, etc.

• It is plausible that TGFBeta signaling islinked to TAA in both syndromic and non-syndromic disease

• Role of angiotensin receptor blockers(Losartan)


Aortic repair in Marfan: Topics of concern

1. Indications

2. Operative technique

3. Recurrent aneurysm

4. Role of TEVAR


Teflon felt reinforcement

Tension free anastomosis

Proximal anastomosis Distal anastomosis


Intercostal patch:↑risk of late aneurysm

Minimized aortic native tissue


Recurrent patch aneurysm


Selective bypass in index procedure


•Male, 27 years old

•Bentall intervention

•Mitral valve repair

Surgical clinical case

Arachnodactyly

Pectus excavatumDolichostenomelia


Aortic involvement

17 cm

Heart

Left kidney

28 cm


Tutto schermo

Left kidney

Heart

Aneurysm

Spleen


TAAA open repair

CT

SMA

RRA

LRAIntercostal

artery


Role of TEVAR in Marfan

•Commonly hostile anatomy

•Aortic/neck dilatation

•Migration

•Retrograde/antegrade dissection

•Recurrent aneurysm


Migration


SINE in Marfan patients: up to 30%


SINE may be antegrade or retrograde into the aortic arch


Distal progression of disease


Open conversion for distal progression


Multiple previous aortic repairs

•Female, 19 years old, 34 Kg

•Acute chest pain

•Ascending, arch and

descending surgical grafts

•Frozen chest

Isthmic anastomotic pseudoaneurysm


Endovascular clinical case

Pseudoaneurysm

exclusion

Post operative CT scan

Custom-made

stentgraft landing into

the previous surgical

grafts


Hybrid or total Endo: “ALL or NONE”


Refer these patients to a Marfan Center

• Medical therapy, follow up

• Screen for genetic disease

• Evaluate family members


Conclusions

• New clinical entities recognized

• Diagnostic criteria revised

• New non surgical therapies tested

• Surgical improvements

30 years of research equaled

30 years of additional life expectancy


Documents

Presentazione di PowerPoint - Società Italiana di ... · defined above) = MFS *without discriminating features of Loeys-Dietz syndrome, vascular EDS or Shprintzen-Goldberg syndrome