Rami Khouzam, MD
DISCLOSURE
The Impossible Dream
INDEX CASE
• 64 y/o WM presented with left- sided CP
for 3 weeks
– sharp, continuous, radiating down his left
arm, not exacerbated by exertion
– NTG SL: some relief
– diaphoresis and palpitations
– (Similar episode 3 months prior)
Past Medical History
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HTN
Diverticulosis, AVMs, Multiple GI bleeds
Hyperlipidemia
Hypothyroidism
Cerebellar stroke1996
Fe. Deficiency anemia
Aortic insufficiency
Atrial fibrillation
Family History
• CAD, HTN in father
• Colon cancer in uncle
Social History
• Tobacco & ETOH (+), quit after CVA
Medications
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Aspirin 81 mg
Plavix 75 mg
Ferrous sulfate 325 mg bid
Synthroid 0.05 mg
Lisinopril 20 mg
Nitroglycerin 0.4 mg SL prn
Omeprazole 20 mg
PE
• Gen: Pale
• Neck: JVD 12 cm
• CV: S1 S2 +S4 Irregular irregularity
3/6 early diastolic murmur LSB apex
• Lungs: Fine bilat. basal crackles
• Abdom: +BS
• Ext: Trace edema bilat.
Labs (pertinent)
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HGB: 11.8 
HCT: 37.2 
MCV 
Ferritin 
TIBC 
Dipsesta (3 months earlier):
• No evidence of ischemia
• EF: 35%. Cardiomyopathy
Cardiac catheterization:
• Normal coronary arteries
• Aortic root 3+-4+ AI
2D- Echo:
• Dilated aortic root with moderate to severe
aortic insufficiency
• LV Diastole: 70 mm
TEE:
• Dilated aortic root at the sinuses of Valsalva
maximun diameter 6.3 cm
• 3-4 + AI
• Mild global hypokinesis. EF ~ 45-50%
CT of Chest/ Abdomen/ Pelvis:
• Dilated aortic root with ectatic
descending thoracic and abdominal
aorta
• No ascending aortic aneurysm
identified beyond the root
Aortic Aneurysms
• Incidence: (thoracic) ~ 5.9 per 100,000
person-years
• Lifetime probability of rupture: 75-80 %
• 5-year untreated survival rates : 10-20%
Size matters…
risk of rupture within 1 year
< 5 cm: 4%
 6 cm: 43%
 8 cm: 80%
PATHOPHYSIOLOGY
• Aneurysm: localized or diffuse aortic
dilatation > 50% normal diameter
• Weakness or defect in the aortic wall
• Cystic medial degeneration  progressive
dilatation
• Atherosclerosis associated but not enough
• Other factors: CTD
CONDITIONS ASSOCIATED
WITH ANEURYSMS
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ADPKD
FMD (Fibromuscular Dysplasia)
AVM
CTD: Ehlers-Danlos type IV, Marfan’s
syndrome, pseudoxanthoma elasticum
• Coarctation of the aorta
• Osler-Weber-Rendu syndrome
• Bacterial endocarditis
SURGICAL TREATMENT
Aortic valve or graft replacement or both,
depends on patient presentation
1970s and 1980s: No longer was any
portion of the aorta beyond reach of the
cardiovascular surgeon
Cooley, Debakey, and others...
• Michael E. DeBakey, M.D., is the
oldest of five children born to
Lebanese immigrants
• Born in 1908, in Lake Charles, LA
• While still a medical student, he
devised a pump that became one
of the essential components of the
heart-lung machine, which made
open-heart surgery possible
• Has performed more than 60,000
cardiovascular procedures
• First to perform successful excision
and graft replacement of arterial
aneurysms
• A pioneer in the development of an
artificial heart, he was the first to use a
heart pump successfully in a patient
• He also conceived the idea of lining a
bypass pump and its connections with
Dacron velour
• DeBakey is currently working with
NASA to develop a self-contained,
miniaturized artificial heart
• His DeBakey-Raytheon-ITS
telemedicine system uses satellites to
electronically link remote sites of the
world to the Texas Medical Center for
medical training and treatment
• Aortic insufficiency causes:
A) Damage of the aortic valve leaflets:
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Rheumatic endocarditis
Trauma
Bicuspid aortic valve
Rheumatoid arthritis
Myxomatous degeneration
Ankylosing spondylitis
Marfan’s syndrome
Phenfluramine-phenteramine
B) Distortion or dilation of the aortic root and
ascending aorta:
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Aortic root dilatation
Systemic hypertension
Syphilis
Reiter’s syndrome
Ankylosing spondylitis
Trauma
Dissecting aneurysm
Elhers-Danlos syndrome
Osteogenesis imperfecta
Pseudoxanthoma elasticum
Inflammatory bowel disease
Annuloaortic ectasia
Severe valvular lesions...
• Until the early 1980s: ONLY surgery
• 1985: Percutaneous aortic valvuloplasty
(PAV) was described by Cribier et al
Circulation, April 2004
Results
• Reduces tight stenosis to moderate:
– final valve area between 0.7 and 1.1 cm2
• (clearly inferior to a valvular prosthesis
usually valve area >1.5 cm2)
Risks
• Hospital mortality from 3.5%-13.5%
within 24 hours, 20%-25% of the
patients at least 1 serious complication
Long-Term Results
• Benefit decreases and finally
disappears after a few months
• It is now recognized that PAV alone
does not change the natural course of
the disease
New Frontiers
Or
New Dead-Ends???
Percutaneous Valve
Replacement & Repair
• Mid 1960s: first experiments started
• 1992: Andersen et al
porcine bioprosthetic valve attached to a
wire stent in pigs’ chest
Followed by other animal models
• 2000: percutaneous pulmonary valve
replacement started in humans with the
report by Bonhoeffer et al
(bovine jugular vein sutured into a stent)
• Lutter et al: similar experiments with a
porcine aortic valve mounted into a selfexpandable nitinol stent
• Satisfactory durability of the devices for a
period up to 2 years
• Late 2002: First percutaneous aortic valve
implantation in humans, performed by
Cribier, in a 57 yo man with severe aortic
stenosis, cardiogenic shock and
contraindications for surgery
• Good valve function: AVA 1.6 cm2
• However, the patient died of severe
extracardiac complications 4 months later
• Since then, 6 other such procedures have
been performed
JACC, March 2004
• Prolonged life expectancy, aging population,
increased number of patients with
degenerative calcific aortic stenosis
who NEED Surgical AVR
• A subset of patients, elderly with declining
health status or life-threatening comorbidities
AVR too high risk or contraindicated
• Limited therapeutic options:
 interest in the development of
percutaneously delivered bioprosthetic
aortic heart valve
• Apr. 2002- Aug. 2003: 6 patients; 5 males and
1 female
• Each patient declined for surgery by cardiac
surgeon
• 3 in cardiogenic shock. All in (NYHA) class IV
• Balloon valvuloplasty previously attempted in
4 cases
• Aspirin (160 mg) and Plavix (300 mg): the day
before the procedure
• Trans-septal catheterization from the right
femoral vein, heparin 5,000 IV
• A 7-F flotation balloon catheter for anterograde
crossing of the aortic valve
• Transseptal puncture dilated with a 10mm balloon catheter, 23 mm balloon
catheter advanced from the right femoral
vein to predilate the native aortic valve
• Through a 24-F sheath PHV advanced
over the wire, across the interatrial
septum within the stenotic native valve
• In 2 patients, rapid cardiac pacing (200 to
220 beats/min) of the right ventricle
during PHV delivery to decrease aortic
blood flow and prevent the risk of PHV
migration during balloon inflation
• Post-procedural treatment included
aspirin (160 mg), plavix (75 mg)
No COUMADIN needed
•  in AVA from 0.49  0.8 cm2 to 1.66  0.13 cm2
(p<0.04)
•  in transvalvular gradient from 38  11 mm Hg
to 5.6  3.4 mm Hg (p<0.04)
• Mean duration of the procedure was 134  23
min. Mean fluoroscopy time was 28  14 min
Clinical Course
• Dramatic clinical improvement
• The initial 3 patients who survived the
procedure (patients 1, 3 & 4) died of noncardiac complication at 18, 4 and 2 weeks
respectively
• Causes of death:
– complications of leg amputation due to longstanding PVD (patient 1)
– abdominal syndrome (patient 3)
– hemorrhage from rectal carcinoma (patient 4)
• The most recent 2 patients were discharged
at days 12 and 15. Clinically stable at 8
weeks with no symptoms of heart failure
Why the anterograde trans-septal approach?
• Several advantages over the retrograde
approach to reach the aortic valve:
– Allows percutaneous insertion of the PHV through
a 24-F sheath in the femoral vein under local
anesthesia
– Eliminates the risk of arterial thrombosis,
dissection or rupture
– Offers more predictable valve delivery (since the
PHV crosses the less diseased myocardial surface
of the aortic leaflets and is coincident with the
direction of blood flow)
• AVA ~ 1.7 cm2 obtained in all successful
cases
• > 3-fold improvement  consistently
associated with a striking early improvement
of the left ventricular function
• Results significantly better than those
obtained after balloon aortic valvuloplasty
which rarely provides  in valve area above
0.8 cm2
Survival & Outcome ??
• In this selected population of severe
aortic stenosis associated with multiple
potentially fatal comorbidities, prolonged
survival is unlikely
• Paravalvular aortic regurgitation noted in
all patients post-PHV implantation
Advantages:
• Bioprosthetic valve with stainless steel stent:
– No NEED for long-term anticoagulation
– ASA & Plavix: enough
• I-REVIVE study: Ongoing pilot clinical trial
will allow further refinement of the technique
and assessment of short and long-term
clinical outcomes
JACC, March 2004
• The technique that will be adopted by the
majority of cardiologists has to be:
– Safe
– Very low risk of mortality & morbidity
– Easy to perform
• The Valve has to be:
– Ideal
– Biocompatible with no long-term morbidity
– Should last preferably for a lifetime but at least
7-10 years
– Expandable (child)
– Economical
• EXCITING new era for percutaneous cardiac
intervention
• If such valves and procedures are proved
safe and effective
Hundreds of thousands of patients with
calcific aortic stenosis & thousands of patients
with pulmonic insufficiency may benefit
? Maybe also…AI
Conclusions
• At the present stage, there are more questions
than answers:
– How can we prevent the obstruction of coronary ostia
and paravalvular leaks in asymmetric calcified
orifices?
– What will be the ideal material?
• Jugular bovine veins are limited in size, their
outcome in the systemic circulation is unknown
• Valves made of polymer or biological material are
to be designed and evaluated
• Lessons from the past suggest that in this
field, a close collaboration between
interventionists and surgeons is of utmost
importance
• First applications of percutaneous aortic
valve replacement in humans opens a new
era for research and potential clinical
application for the percutaneous treatment
of acquired valve disease
• Zeus made Pandora, the first
mortal woman, because he was
mad at Prometheus who had
had given the mortals special
gifts, so he decided to give them
one more: Pandora
• Each god gave her something to
make her perfect. Venus gave
her beauty, Mercury gave her
persuasion, Apollo gave her
music, Hephaestus gave her
voice, Hermes gave her
pettiness in her tiny brain, etc.
Finally she was ready for Earth
• Zeus gave her to Epimetheus
(Prometheus' brother)
• Prometheus had said to
Epimetheus not to take anything
from the Olympians, especially
Zeus
• Epimetheus was about to
decline, but as soon as he
looked at her and saw her
beauty, he accepted Zeus' gift
• Epimetheus gave Pandora a box
that she was forbidden to open
• Every day Pandora wondered
what was in the box
• She knew she mustn't open it,
but she was extremely curious
and could not bear not to know
its contents
• As soon as she pulled the cover
off, all of the evil and mistrust
flew out into the world
• When Pandora looked at the
bottom of the box, she saw that
the only thing left was hope to
Comfort mankind
From a
DREAM..
To a
REALITY ??