rami khouzam, md. disclosure the impossible dream

63
Rami Khouzam, MD

Upload: august-hubbard

Post on 24-Dec-2015

222 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Rami Khouzam, MD

Page 2: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

DISCLOSURE

The Impossible Dream

Page 3: 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)

Page 4: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Past Medical History

• HTN

• Diverticulosis, AVMs, Multiple GI bleeds

• Hyperlipidemia

• Hypothyroidism

• Cerebellar stroke1996

• Fe. Deficiency anemia

• Aortic insufficiency

• Atrial fibrillation

Page 5: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Family History• CAD, HTN in father

• Colon cancer in uncle

Social History• Tobacco & ETOH (+), quit after CVA

Page 6: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Medications

• 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

Page 7: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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.

Page 8: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Labs (pertinent)

• HGB: 11.8 • HCT: 37.2 • MCV • Ferritin • TIBC

Page 9: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 10: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Dipsesta (3 months earlier):

• No evidence of ischemia

• EF: 35%. Cardiomyopathy

Cardiac catheterization:

• Normal coronary arteries

• Aortic root 3+-4+ AI

Page 11: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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%

Page 12: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

CT of Chest/ Abdomen/ Pelvis:

• Dilated aortic root with ectatic descending thoracic and abdominal aorta

• No ascending aortic aneurysm identified beyond the root

Page 13: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Aortic Aneurysms

• Incidence: (thoracic) ~ 5.9 per 100,000 person-years

• Lifetime probability of rupture: 75-80 %

• 5-year untreated survival rates : 10-20%

Page 14: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Size matters…

risk of rupture within 1 year

< 5 cm: 4% 6 cm: 43% 8 cm: 80%

Page 15: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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

Page 16: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

CONDITIONS ASSOCIATED WITH ANEURYSMS

• 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

Page 17: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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...

Page 18: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 19: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 20: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• Aortic insufficiency causes:

A) Damage of the aortic valve leaflets:• Rheumatic endocarditis• Trauma• Bicuspid aortic valve• Rheumatoid arthritis• Myxomatous degeneration• Ankylosing spondylitis• Marfan’s syndrome• Phenfluramine-phenteramine

Page 21: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

B) Distortion or dilation of the aortic root and ascending aorta:

• 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

Page 22: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Severe valvular lesions...

• Until the early 1980s: ONLY surgery

• 1985: Percutaneous aortic valvuloplasty (PAV) was described by Cribier et al

Circulation, April 2004

Page 23: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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)

Page 24: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Risks

• Hospital mortality from 3.5%-13.5% within 24 hours, 20%-25% of the patients at least 1 serious complication

Page 25: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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

Page 26: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 27: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

New Frontiers

Or

New Dead-Ends???

Page 28: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 29: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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

Page 30: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 31: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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 self-expandable nitinol stent

Page 32: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 33: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 34: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

JACC, March 2004

Page 35: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 36: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• Limited therapeutic options:

interest in the development of percutaneously delivered bioprosthetic aortic heart valve

Page 37: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 38: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 39: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 40: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• Transseptal puncture dilated with a 10-mm 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

Page 41: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 42: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 43: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 44: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 45: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 46: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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

Page 47: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

Clinical Course

• Dramatic clinical improvement

• The initial 3 patients who survived the procedure (patients 1, 3 & 4) died of non-cardiac complication at 18, 4 and 2 weeks respectively

Page 48: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• Causes of death:

– complications of leg amputation due to long-standing 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

Page 49: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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)

Page 50: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 51: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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

Page 52: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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

Page 53: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

JACC, March 2004

Page 54: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 55: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 56: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

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

Page 57: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 58: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 59: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 60: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

• 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

Page 61: Rami Khouzam, MD. DISCLOSURE The Impossible Dream

From a DREAM..

To a REALITY ??

Page 62: Rami Khouzam, MD. DISCLOSURE The Impossible Dream
Page 63: Rami Khouzam, MD. DISCLOSURE The Impossible Dream