Transcript Amenophis IV, Lincoln, Paganini, and Rachmaninov Shadwan Alsafwah, MD Cardiology Fellow Staff Support: Dr.

Amenophis IV, Lincoln, Paganini, and Rachmaninov
Shadwan Alsafwah, MD
Cardiology Fellow
Staff Support: Dr. Richard Davis
The University of Tennessee at Memphis
Case
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21 YO AAM presented to the ED with headache,
neck pain, and N/V for 2 days getting worse with
time. The family noticed him to be starting to
develop mental status changes with lethargy and
difficulty following commands.
In ER, LP was done, was found later to have viral
meningitis and was admitted to MICU, and
started on IV Acyclovir.
He had significant improvement, and transferred
to the floor.
on the 3rd hospital day he developed mild
pleuretic CP on ambulation, so repeat ECG
showed significant changes in comparison to
admit ECG, so Cardiology consult requested,
transferred to telemetry, and CEs checked.
Case
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PMH: none
PSH: Skin graft to LLQ (burn)
SH: previous smoker, previous Marijuana, none
recently
No ETOH
FH: Aunt with DM
Meds: Acetaminophen, IV Acyclovir
Allergies: none
ROS: positive for N/V, HA, neck pain, and chills
negative for SOB, visual complaints
excellent exercise tolerance prior to this admit
Case
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PE: on the 3rd hospital stay
General: mildly lethargic, H: 6 00, W: 132 LBS
Vitals: 110/60, 45, 16, 100, 97% on RA
Neck: no JVD, mild nuchal rigidity
Chest: CTAB
CVS: Bradycardic, RRR, no S3 or S4, mid systolic click
heard widely all over the precordium that moved
toward S2 with squatting, and toward S1 with
standing. There was also II/VI early decrescendo diastolic
murmur at LSB
Abdomen: Soft, NT, ND, NABS, + graft scar
Ext: no edema, clubbing, cyanosis
Muskeloskeletal system: without gross abnormalities
Neuro: mildly lethargic, but oriented x3, no focal deficits
Labs and Diagnostic Imaging
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UDS: negative
Head CT: negative
MRI of head and whole spine was negative
CEs obtained when the ECG changes were noted:
1st
2nd
3rd
CKMB
6.6
4.0
2.2
CKMB index 0.8
0.8
1.3
Trop-I
0.07
0.07
0.02
With the positive CEs, 2D echo was requested to
assist in the diagnosis
2D Echocardiogram
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Chambers: Normal LV size and systolic
function, EF is 65-70%
Mild mitral valve prolapse with mild mitral
regurgitation
Annuloaortic ectasia with aortic valve
prolapse and moderate aortic insufficiency
No evidence of aortic dissection
Findings consistent with connective tissue
disorder such as Marfan’s syndrome
Marfan Syndrome (MFS)
Outline
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Incidence
Historic Background
Genetic Background
Pathogenesis
Clinical Manifestations
Diagnosis
Marfan Related
Disorders
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Overlap Heritable
Connective Tissue
Disorder
Prognosis
Management
Pregnancy
Conclusion
Incidence
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In the US it affects 1 in 10,000
At least 200,000 people in the US have MFS or a
related connective tissue disorder
This makes MFS one of the most common singlegene malformation syndromes
May be diagnosed prenatally, at birth, or well into
adulthood
Internationally, no geographic predilection is
known
It is pan-ethnic
No gender predilection is known
Historic Background
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In 1896 Marfan
described the case of
5-year old patient:
Gabriel P.
Weve in 1931
described its
autosomal dominant
inheritance
Dietz in 1991
described FBN1 gene
mutation as the cause
of Marfan syndrome
Antoine Marfan, MD
1858-1942
Amenophis IV
Lincoln
Paganini
Rachmaninov
Genetic Background
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Inherited connective tissue disorder
transmitted as an autosomal dominant
trait
75% of patients have an affected parent
The other 25% is due to new mutations
Most of the time results from molecular
defects in the fibrillin-1 (FBN1) gene
located on chromosome 15q21.1
FBN1 Gene
FBN1 is a large gene composed of 9000 nucleotides dispersed in 65 exones
located at chromosome 15q-21.1
Genetic Background
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Different mutations involving FBN1 gene, but
associated with similar phenotypes have been
demonstrated
However, FBN1 mutations occur across a wide
range of milder phenotypes that overlap the
classic Marfan phenotype
In a minority of cases of typical MFS, a mutation
in FBN1 is not identified. In some of these cases
an inactivating mutation in a gene encoding a
receptor for transforming growth factor-beta
(TGFR2) may be responsible for up to 10% of
Marfan syndrome
Genetic Background
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The first report of an FBN1 mutation was in 1991
By 1998 a total of 137 FBN1 mutations has been
characterized in patients MFS
The majority of these occur as isolated mutations
throughout the gene
To date, no correlation between the specific type
of FBN1 mutation and the clinical phenotype has
been recognized
Mutation analysis can identify the exact mutation
in the fibrilin gene, and linkage analysis can track
an abnormal fibrilin gene in a family. However, no
molecular diagnosis is currently available
commercially. No single gene probe or group of
probes is available to detect most FBN1
mutations
Pathogenesis
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The fibrillin-1 (FBN1)
gene encodes the
glycoprotein fibrillin, a
major building block
of microfibrils
The microfibrils
constitute the
structural components
of the suspensory
ligaments of the lens,
and serve as a
substrates for elastin
in the aorta and the
other connective
tissues
The Functions of Microfibrils
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They act as a scaffolding for the elastic fiber
formation
They are extensible, and may contribute to the
mechanical properties of the mature elastic
tissues by means of load redistribution between
individual elastic fibers
They provide structural anchorage in non-elastic
tissues, such as ciliary zonules
They may serve to anchor endothelial cells and
epithelial cells to elastic fibers of the ECM via cell
binding domains
A role for the microfibrils in the provision of a
flexible mechanical anchor at epithelialmesenchymal basement membrane interfaces,
has been proposed
Pathogenesis
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Production of abnormal fibrillin-1 monomers from
the mutated gene disrupts the multimerization of
fibrillin-1 and prevents microfibril formation
This pathogenetic mechanism has been termed
dominant-negative because the mutant fibrillin-1
disrupts microfibril formation even though normal
fibrillin is being encoded on the other fibrillin
gene
This leads to fragmentation and disorganization
of the elastic fibers in the aortic media and other
connective tissues (inappropriately called cystic
medial necrosis)
Pathogenesis
Mucin
stain of the wall of the aorta demonstrates cystic medial necrosis,
typical for Marfan's syndrome and causes the connective tissue weakness
that explains the aortic dissection. Pink elastic fibers, instead of running in
parallel arrays, are disrupted by pools of blue mucinous
(mucopolysaccharide) ground substance, these accumulations are the socalled “cysts” of cystic medial necrosis.
Manifestations
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Wide range of clinical
severity associated with
MFS
Classically it has
muskeloskeletal, occular,
and cardiovascular
abnormalities
MFS patients also
demonstrate significant
involvement of lung, skin,
CNS
A severe and rapidly
progressive form of MFS
may present at birth
Muskeloskeletal Manifestations
Pectus excavatum
Reduced upper to lower body segment ratio
Arm span/height ratio>1.05
Arms and legs unusually long in proportion to
torso (dolichostenomelia)
Reduced extension of elbows<170
Pectus carinatum
Muskeloskeletal Manifestations
Joint hypermobility
Steinberg (thumb) sign
Arachnodactyly
Highly arched palate
Walker (wrist) sign
Muskeloskeletal Manifestations
Pes planus
Kyphosis
Scoliosis
Ocular Manifestations
Ectopia Lentis: the lens dislocation is usually bilateral, symmetrical and upward
Other Ocular Manifestations
Nuclear sclerotic cataract
Hypoplastic iris
Myopia due to increased
axial length of the globe
Retinal detachment
Dura
Dural Ectasia
Pulmonary Manifestations
Spontaneous pneumothorax
Apical pulmonary blebs
Skin Manifestations
Striae atrophicae
Incisional Hernia
Cardiac Manifestations in Marfan
Syndrome
Outline
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Incidence
Mitral valve involvement
Aortic root involvement
Aortic dissection
Other cardiac manifestations
Cardiac Manifestation
Incidence
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The most common cardiovascular features
are MVP and dilation of sinuses of Valsalva
Associated clinical problems of mitral
regurgitation, aortic regurgitation, and
aortic dissection account if untreated for
most of early mortality that results in an
average age of death in the fourth decade
of life
Children tend to be more severely affected
by mitral valve disease; whereas aortic
disease is progressive and more likely in
adolescence and beyond
Mitral Valve Involvement in MFS
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MVP is age dependent
More common in
females
Incidence reaches 6080% when patients
are studied by 2D
echo
The valve leaflets
have an elongated and
redundant appearance
Mitral Valve Involvement in MFS
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Progression in severity as judged by the
appearance of or worsening of MR by
clinical and echo criteria occurs in at least
25% of patients (a much higher rate in
compared to MVP in the general
population)
The mitral annulus dilates and contributes
to the regurgitation, as do stretching and
occasional rupture of chordae
10% of patients with marked prolapse
have calcification of mitral annulus
Aortic Root Involvement in Marfan
Syndrome
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The sinuses of Valsalva are
often dilated at birth
Dilation of the aorta is
found in 50% of children
with Marfan and will
progress with time
60-80% of adults with
Marfan have dilation of the
aortic root, often with
aortic regurgitation
The rate of progression
varies widely among
patients in general, thus
predicting long term risks
of developing aortic
regurgitation is fraught
with uncertainty.
Aortic Root Involvement in Marfan
Syndrome
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AI often appear in adults at a
diameter of 50 mm, but may
be absent at diameter of
more than 60 mm
The aortic dilation is limited to
the ascending aorta. Hence,
TTE is sufficient for detecting
and monitoring changes in
aortic root diameter
The rate of aortic diameter
change is slow, measured in
millimeters per year
Patients with dilation less
than 1.5 times the mean
diameter predicted for their
body size can be observed
annually, but as the diameter
increases, the wall tension
increases, and more frequent
evaluation is necessary
Why does wall tension increase with radius?
If the upward part of the fluid pressure remains the same, then the downward
component of the wall tension must remain the same. But if the curvature is less, then
the total tension must be greater in order to get that same downward component of
tension.
LaPlace's Law
The larger the vessel radius, the larger the wall tension
required to withstand a given internal fluid pressure.
For a given vessel radius and internal pressure, a spherical
vessel will have half the wall tension of a cylindrical vessel.
Pascal's principle requires that the pressure is everywhere the same inside the
balloon at equilibrium. But examination immediately reveals that there are great
differences in wall tension on different parts of the balloon. The variation is
described by Laplace's Law.
Aortic Dissection in Marfan
Syndrome
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Marfan is the cause of 50% of aortic dissections
occurring before the age of 40, compared to only
2% of older patients
The risk of dissection increase with the size of the
aorta.
Many patients with Marfan and aortic dissection
have a family history of dissection
Fortunately occurs infrequently below a diameter
of 55 mm in adults
Hence, many physicians have adopted the criteria
of 50 to 55 mm maximal aortic root dimension
for performing elective surgery in Marfan
regardless of the severity of AI.
Marfan patient’s with family history of aortic
dissection should have the surgery with the Aortic
root max diameter of 50 mm
Aortic Dissection in Marfan
Syndrome
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Usually begins just above
the coronary ostia, and
extends the entire length
of the aorta
About 10% of dissections
begin distal to the left
subclavian artery
Rarely, the dissection is
limited to the abdominal
aorta
Not all acute dissections in
patients with Marfan
involve severe tearing
chest pain radiating to the
back, as some extensive
dissections have been
occult, reinforcing the need
for a high level of suspicion
by physicians
Other Cardiac Manifestations
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Arrhythmias:
Ventricular
Supraventricular: often associated with chronic MR
LV dysfunction:
occasional patients with Marfan syndrome who have no
clinically important valvular abnormalities develop
moderate-severe LV dysfunction
-Could represent the unlikely coincidence of Marfan
syndrome and IDCM
-there has been evidence that certain fibrillin mutations
could have detrimental effect on the myocardial
function
Further studies are needed
Diagnosis
The Berlin Criteria
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Was implemented in 1988
MFS diagnosis was based on involvement of skeletal
system and two other systems
and at least 1 major manifestation:
Ectopia lentis
Aortic dilation or dissection
Dural ectasia
Because some of the symptoms and signs of Marfan
(such as joint hypermobility) are much more often seen
in patients without the disease, this has led to a
recognized tendency to overdiagnose Marfan syndrome in
index cases or family members
Furthermore, no Family history or molecular data were
incorporated in the diagnosis
Diagnosis
Ghent criteria
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Was implemented in 1996, and have
incorporated molecular data and family
history, to the clinical data
More stringent: about 19% of patients
diagnosed under Berlin criteria did not
meet the Ghent criteria
Note that some of the criteria used to diagnosis Marfan
syndrome arise with age. Therefore, a child may fail to
meet the criteria at first, but may have manifestations
that definitely meet the criteria at a later date. This
phenomena of partial expression of Marfan syndrome in a
child that one suspects will meet the full criteria at an
older age has been termed "emerging Marfan syndrome".
Diagnosis
Ghent criteria
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The diagnosis is made if:
- In family members: presence of major
involvement in 1 organ system as well
as involvement in a second organ
system
- If the family and genetic histories are
not contributory: major criteria in 2
different organ systems and
involvement of a third organ system are
required
System
Major Criteria
Presence of at least four of the
following manifestations
* Pectus excavatum of moderate
severity
* Pectus carinatum
* Joint hypermobility
* Pectus excavatum requiring surgery
* Highly arched palate with crowding
of teeth
* Reduced upper to lower segment
ratio or arm span to height ratio
greater than 1.05
Skeletal
System
Minor Criteria
* Wrist and thumb signs
* Facial appearance (dolichocephaly,
malar hypoplasia, enophthalmos,
retrognathia, down-slating palpebral
fissures)
* Scoliosis > 20d or spondylolisthesis
* Reduced extensions at the elbows
(<170d)
* Medial displacement of the medial
malleolus causing pes planus
* Protrusio acetabulae of any degree
(ascertained on radiographs)
* Ectopia lentis (dislocated lens)
Ocular
System
* Abnormally flat cornea (as measured
by keratometry)
* Increased axial length of globe (as
measured by ultrasound)
System
Major Criteria
Cardiovascul
ar System
* Mitral valve prolapse with or
without mitral valve regurgitation
* Dilatation of the ascending aorta
with or without aortic
regurgitation and involving at
least the sinuses of Valsalva; or;
* Dissection of the ascending
aorta
Pulmonary
System
Minor Criteria
None
* Dilatation of the main pulmonary
artery, in the absence of valvular or
peripheral pulmonic stenosis or any
other obvious cause, below the age
of 40
* Calcification of the mitral annulus
below the age of 40
* Dilatation of dissection of the
descending thoracic or abdominal
aorta below the age of 50
* Spontaneous pneumothorax
* Apical blebs (ascertained by chest
radiography)
Skin and
Integument
None
* Stretch marks not associated with
marked weight changes, pregnancy
or repetitive stress
* Recurrent incisional hernias
System
Major Criteria
Dura
Minor Criteria
None
* Lumbosacral dural ectasia by
CT or MRI
Family/Genet
ic History
None
* Having a parent, child or sibling
who meets these diagnostic
criteria independently
* Presence of a mutation in FBN1
known to cause the Marfan
syndrome
* Presence of a haplotype around
FBN1, inherited by descent,
known to be associated with
unequivocally diagnosed Marfan
syndrome in the family
American Journal of Medical Genetics 62:417-426, 1996
Marfan Related Disorders
Symptom Overlap with Marfan Syndrome
Mutation in
Fibrillin-1 Gene?
Familial Aortic Aneurysm
Aortic enlargement and dissection, Variable skeletal
findings
Generally not
Bicuspid Aortic Valve with
Aortic Dilation
Aortic enlargement and/or dissection
unknown
Familial Ectopia Lentis
(Dislocated Lens)
Eye lens dislocation
Common skeletal findings
Yes
MASS phenotype, Mitral
Valve Prolapse, Myopia
Borderline aortic enlargement
Skin and skeletal findings
At least
sometimes
Skeletal Features (Marfan
Body Type)
Skeletal findings
At least
sometimes
Mitral Valve Prolapse
Syndrome
Mitral valve prolapse
Variable skeletal findings
At least
sometimes
Congenital Contractural
Arachnodactyly (CCA or
Beals syndrome)
Mitral valve prolapse
Variable skeletal findings
No (FBN-2
mutation)
Myopia Retinal detachment
Joint hypermobility or contracture
Scoliosis
Mitral Valve Prolapse
No (Collagen
genes
mutation)
Condition
Stickler Syndrome
Shprintzen-Goldberg
Syndrome
Aortic enlargement
Skin and skeletal findings
Rare
Ehlers-Danlos Syndrome
Skin and skeletal findings
Aortic enlargement/dissection in selected types only
No (Collagen
gene mutation)
Homocystinuria
Mitral Valve Prolapse
Eye lens dislocation
Skin and skeletal findings
No (metabolic
disorder)
Overlap Heritable Connective
Tissue Disorder
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According to a study at Johns Hopkins, more than
half of all patients evaluated in their clinic for the
possible diagnosis of a heritable disorder of
connective tissue could not be determined to
have any specifically defined disorder.
In spite of that, those patients had considerable
clinical evidence of a systemic defect of the
extracelular matrix (MVP, Aortic root dilatation,
muskeloskeletal abnormalities…)
The authors described these patients as having
an "overlap disorder".
They suggest that there is a continuum of
connective disorder symptoms with mitral valve
prolapse at the mild end and Marfan syndrome at
the more severe end.
Prognosis
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The life span of untreated patients with the classic MFS was
about 32 years in 1972
Improved therapy has resulted in marked increase in life
expectancy up to 61 years in 1996
Cardiovascular disease, especially aortic dilation and
dissection is the major cause of morbidity and mortality
Progression from MVP to MR is the most common cause of
infant morbidity
Aortic dissection is uncommon in childhood and adolescence
Death after infancy usually involves ascending aortic
dissection and chronic AI
For reasons that are not well understood, life expectancy is
significantly lower in men than women
A family history of premature death or aortic surgery may
identify patients at increased risk
Management
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Beta Blockers
Restriction of strenuous physical activities
Monitoring of the aortic root size
Elective surgical repair of the aorta
SBE prophylaxis
Correctional ophthalmologic and
orthopedic surgeries
Management during pregnancy
dp/dtmax
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It has been suggested that the
shape of the pulse wave (rate
of change in the central
arterial pressure with respect
to time designated as dp/dt) is
the most important initiator of
the force which acts on the
aortic wall to cause extension
and rupture of acute
dissecting aneurysms
To test this, a standard model
of the aorta was constructed,
using tygon tubing with rubber
cement lining
An “intimal tear” was
produced and aortic model
was subjected to nonpulsatile
and pulsatile flow
Prokop EK, et al. Circ Res 1970;27:121-127
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The aortic models were
first subjected to a steady
flow of water at rates
starting at 500 ml/min,
and increasing in
increments to a max 6000
ml/min
Then the flow was held
constant at 2500 ml/min,
the initial pressure was 50
mm Hg. The pressure was
then increased in
increments by changing
the resistance in the distal
tube, until a final pressure
of 250 mm Hg was
reached
Pressure waveforms were
measured through catheter
Prokop EK, et al. Circ Res 1970;27:121-127
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The aortic models was
then subjected to pulsatile
flow. With pumping rate
70 strokes/min, with
systole being 60% and
diastole 40% of the entire
cycle
The rate of dissection was
calculated by recording
the time necessary to
dissect the intimal lining
from the Tygon tubing
(cm/min)
The aortic model was
subjected to a step
increase of dp/dtmax. This
was accomplished by
changing the systolediastole time ratio of the
pulsatile pump
Prokop EK, et al. Circ Res 1970;27:121-127
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The same experiment were
performed on dog aorta models
The descending aortas were
removed from 15 sacrificed dogs
the aorta was subjected to
nonpulsatile flow, with
incremental increase in peak
systolic pressure until a final
pressure of 175 mm Hg was
reached
The aorta was then subjected to
pulsatile flow at rate 60
strokes/min.
Then the aortas were subjected
to step increase in dp/dtmax
The presence of dissection were
noted every 3 min or until the
vessel ruptured
Prokop EK, et al. Circ Res 1970;27:121-127
Results
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With nonpulsatile flow alone (97 experiments) no
dissection occurred at pressures up to 400 mm
Hg
Pulsatile flow produced rapid and usually
complete dissection with a maximum systolic
pressure of 120 mm Hg
The extent of dissection per pulse was related to
dp/dtmax
No dissection occurred until a critical value of
dp/dtmax (790 mm Hg/sec) was reached
Similar results were obtained with dog aortas
The rationale for decreasing dp/dtmax as a
worthwhile method of therapy in acute dissective
aneurysms of the aorta is supported by this study
Prokop EK, et al. Circ Res 1970;27:121-127
Prokop EK, et al. Circ Res 1970;27:121-127
Beta Blockers
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Recommended in all patients with Marfan
including children unless contraindicated
Propranolol was the BB found to have a
beneficial effect on slowing aortic dilation,
but other BB may be used as well
The dose should be adjusted to maintain
the heart rate at 110 beats/minute after
submaximal exercise
In pregnancy, labetolol is the preferred
BB, as atenolol may impair fetal growth
If intolerance to BB, then CCB may be
used
Beta Blockers
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An NIH-funded, open-label, randomized trial of propranolol in 70
adolescent and adult patients with classic Marfan’s syndrome:
32 treated
38 untreated (control)
Done at the center for Medical Genetics, Johns Hopkins University,
Baltimore
The Aortic-root dimensions, and clinical end points were
monitored:
Aortic regurgitation
Aortic dissection
Cardiovascular surgery
CHF
Death
Average f/u:
10.7 years in the treatment group
9.3 years in the control group
The dose of propranolol was individualized; the mean dose was
212+-68 mg per day
Shores, J, et al. N Eng J Med 1994;330:1335
(The aortic ratio is obtained by dividing the
measured aortic diameter by the diameter
predicted from the patient height, weight,
and age)
P<0.001
Empirical Distribution Functions of the
Rate of Change in the Aortic Ratio
The height of each curve at any point shows the
proportion of patients with values at or below
the value given on the x axis
Changes in the Aortic Ratio in the Treatment
Group and the Control Group.
Shores, J, et al. N Eng J Med 1994;330:1335
Numbers of patients who reached
clinical end points and their initial
aortic ratios.
Kaplan-Meier survival analysis based on
the clinical end points in the Study (death,
CHF, AI, aortic dissection, cardiovascular
surgery)
Shores, J, et al. N Eng J Med 1994;330:1335
Monitoring of the Aortic root
Size
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The recommended threshold for elective surgery
for aortic root dilation in adults is 50 mm
In adults yearly sonographic measurement of
aortic root diameter is recommended if the aortic
root size is <45 mm. Twice yearly monitoring
should be performed for those with diameters
45 mm
In children, it has been suggested that the aortic
root dimensions be plotted serially against BSA,
and an operation be considered if the diameter
begin to increase rapidly from a previously stable
percentile even if the absolute measurement is
less than 50 mm. Also, an increase of >10
mm/year is regarded as rapid enlargement in
children
Elective replacement of aortic root
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In a series of 675
patients from Johns
Hopkins, the 30 day
mortality was studied
for:
-elective repair
-urgent repair
(within 7 days of
surgical consultation)
-emergency repair
(within 24 hour of
surgical consultation)
Gott, VL, et al. N Engl J Med 1999;340:1307
Gott, VL, et al. N Engl J Med 1999;340:1307
Kaplan–Meier Survival Analysis of 675 Patients with Marfan's Syndrome,
According to the Urgency of the Procedure. I bars are 95 percent confidence intervals
Gott, VL, et al. N Engl J Med 1999;340:1307
Pregnancy
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Women with Marfan syndrome who are contemplating surgery
should have a screening TTE to assess aortic root dimension
Elective repair before conception is recommended if the diameter
is  50 mm
Pregnancy should be discouraged if the diameter is  40 mm
If the diameter is <40, then:
-Careful clinical and echocardiographic monitoring
-BB should be given (labetolol is preferred)
-Epidural anesthesia to minimize pain during vaginal
delivery
-Surgical aortic repair during pregnancy should be
considered if there is progressive dilation of the aortic
root during gestation. Discussion of possible surgical
intervention is appropriate when the aortic root diameter
is 55 mm or at an earlier time if the aortic root is
dilating rapidly
Summary
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The diagnosis of MFS is based on the presence of characteristic
skeletal, cardiovascular, and ocular findings in familial and
sporadic cases. Although it is possible to identify mutations
involving the FBN1 and TGFBR2 genes in many MFS patients,
these genetic tests are not necessary for routine clinical diagnostic
purposes
Monitoring the aortic root diameter using U/S is recommended as
a means of identifying patients at risk for aortic dissection. In
adults, yearly U/S is recommended as long as the aortic root
diameter is <45 mm. Twice yearly if 45 mm
Restriction of physical activity, and BB are essential treatment
modalities
Because elective aortic repair is associated with reduced mortality
in comparison to urgent or emergent repair, it should be
considered when the aortic root is 50 mm
Women with MFS who are contemplating pregnancy should have a
TTE. If the aortic root diameter is 40 mm then the pregnancy is
strongly discouraged. If the diameter is <40 then close monitoring
is recommended
Thank you