Polymeric Materials and Artificial Organs - ACS Publications

8 The Current Status of Prosthetic Heart Valves AJIT P. YOGANATHAN, E. C. HARRISON, and R. H. FRANCH Bio Fluid Dynamics Laboratory, School of Chemical Engineering, Georgia Institute of

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Technology, Atlanta, GA 30332

The main objective of the study is to correlate the i n v i t r o fluid dynamic performances o f prosthetic heart valves with t h e i r i n vivo clinical and pathological c h a r a c t e r i s t i c s . The aim is to c l e a r l y document any r e l a t i o n s h i p s between i n vitro f l u i d dynamic performance and potential clinical and/or pathological findings and complications. Heart valve prostheses have been used successfully since 1960. Of the nearly 50 d i f f e r e n t cardiac valves introduced over the past 22 years, many have been discarded due to t h e i r lack o f success, and o f those remaining, several modifications have been made. The most commonly used basic types of prosthetic valves are: (a) caged ball, (b) tilting d i s c , (c) caged d i s c , (d) bi-leaflet and (e) bioprostheses. The most serious problems and complications a s s o c i ated with valve prostheses are: (a) thromboembolism, (b) tissue overgrowth, (c) i n f e c t i o n , (d) tearing of sewing sutures, (e) hemolysis, (f) valve f a i l u r e due to material fatigue or chemical change, (g) damage to the endothelial tissue l i n i n g o f the vessel wall adjacent to the v a l v e , (h) large pressure gradients e s p e c i a l l y under exercise c o n d i t i o n s , and (i) excess r e g u r g i t a t i o n . Problems ( a ) , ( b ) , ( e ) , (g) - ( i ) are directly related to the fluid dynamics associated with the d i f f e r e n t prosthetic valve designs, and are discussed i n d e t a i l i n t h i s paper. H e a r t v a l v e p r o s t h e s e s have been used s u c c e s s f u l l y s i n c e 1 9 6 0 . A s s t a t e d b y R o b e r t s {Vj t h e d e c a d e o f 1 9 6 0 w i l l p r o b a b l y b e remembered most i n t h e a n n a l s o f c a r d i o l o g y as t h e decade d u r i n g w h i c h c a r d i a c v a l v e r e p l a c e m e n t became a s u c c e s s f u l r e a l i t y . O f t h e n e a r l y 50 d i f f e r e n t c a r d i a c v a l v e s i n t r o d u c e d o v e r t h e p a s t 2 2 y e a r s , many have b e e n d i s c a r d e d d u e t o t h e i r l a c k o f s u c c e s s , a n d o f t h o s e r e m a i n i n g , s e v e r a l m o d i f i c a t i o n s h a v e b e e n made o r 0097-6156/84/0256-0111$11.00/0

© 1984 American Chemical Society

Gebelein; Polymeric Materials and Artificial Organs ACS Symposium Series; American Chemical Society: Washington, DC, 1984.


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a r e b e i n g made a t t h e t i m e o f t h i s w r i t i n g . The most commonly used b a s i c t y p e s o f p r o s t h e t i c v a l v e s a t p r e s e n t a r e (a) caged b a l l , (b) t i l t i n g d i s c , (c) caged d i s c , (d) b i - l e a f l e t and (e) bioprostheses. At present over 75,000 p r o s t h e t i c v a l v e s of d i f f e r e n t d e s i g n s are used a n n u a l l y throughout the w o r l d . Even a f t e r 20 y e a r s o f e x p e r i e n c e t h e p r o b l e m s a s s o c i a t e d w i t h h e a r t v a l v e p r o s t h e s e s have not been t o t a l l y e l i m i n a t e d . The most s e r i o u s problems and c o m p l i c a t i o n s a s s o c i a t e d w i t h h e a r t valve prostheses are: (a) t h r o m b o e m b o l i s m , (b) t i s s u e o v e r g r o w t h , (c) i n f e c t i o n , (d) t e a r i n g o f s e w i n g s u t u r e s , (e) r e d c e l l destruct i o n ( h e m o l y s i s ) , ( f ) v a l v e f a i l u r e due t o m a t e r i a l f a t i g u e o r c h e m i c a l c h a n g e , (g) damage t o t h e e n d o t h e l i a l t i s s u e l i n i n g o f t h e v e s s e l w a l l a d j a c e n t t o t h e v a l v e and (h) l e a k s c a u s e d by f a i l u r e of the valve to c l o s e p r o p e r l y . Problems ( a ) , (b), (e) and (g) a r e d i r e c t l y r e l a t e d t o t h e f l u i d d y n a m i c s a s s o c i a t e d w i t h t h e v a r i o u s p r o s t h e t i c h e a r t v a l v e s , a n d n e e d t o be a d d r e s s e d i n more d e t a i l by i n v e s t i g a t o r s s t u d y i n g b i o - f l u i d mechanics. The o t h e r p r o b l e m s a r e i n d i r e c t l y r e l a t e d t o t h e f l u i d mechanics. The p r o b l e m s r e l a t i n g t o v a l v e f a i l u r e due t o m a t e r i a l f a t i g u e o r c h e m i c a l c h a n g e a l s o n e e d t o be s t u d i e d e s p e c i a l l y as t h e y r e l a t e t o b i o p r o s t h e s e s . T i s s u e b i o p r o s t h e s e s g a i n e d w i d e s p r e a d use d u r i n g the m i d 1970' s . I t was e v e n n a i v e l y t h o u g h t by some o f t h e t i s s u e v a l v e m a n u f a c t u r e r s t h a t t h e i d e a l h e a r t v a l v e p r o s t h e s i s had been discovered. The m a j o r a d v a n t a g e o f t i s s u e b i o p r o s t h e s e s comp a r e d t o t h e i r m e c h a n i c a l c o u n t e r p a r t s i s t h a t t h e y have a l o w e r incidence of thromboembolic complications. Therefore, tissue v a l v e s f o r a l a r g e p a r t c a n be u s e d w i t h o u t anticoagulation therapy to e l i m i n a t e or reduce thromboembolic complications. U n f o r t u n a t e l y , the t i s s u e b i o p r o s t h e s e s c l i n i c a l l y used at p r e s e n t a l s o have major d i s a d v a n t a g e s such a s : (a) relatively l a r g e p r e s s u r e d r o p s c o m p a r e d t o some o f t h e m e c h a n i c a l v a l v e s , e s p e c i a l l y i n t h e s m a l l e r s i z e s , (b) j e t - l i k e f l o w t h r o u g h the v a l v e l e a f l e t s , (c) m a t e r i a l f a t i g u e and/or wear o f valve l e a f l e t s , (d) c a l c i f i c a t i o n o f v a l v e l e a f l e t s , e s p e c i a l l y i n c h i l d r e n and young a d u l t s . Because o f t h e s e and o t h e r d r a w b a c k s , v a l v e m a n u f a c t u r e r s a r e now d e v e l o p i n g new d e s i g n s o f m e c h a n i c a l v a l v e s s u c h as t h e S t . J u d e , H a l l - K a s t e r and O m n i - S c i e n c e p r o s t h e s e s , newer d e s i g n s o f b i o p r o s t h e s e s and t r i l e a f l e t v a l v e s made f r o m p o l y m e r i c m a t e r i a l s . The i d e a l h e a r t v a l v e p r o s t h e s i s has n o t y e t been d e s i g n e d and p r o b a b l y w i l l n e v e r e x i s t . An i d e a l v a l v e s h o u l d h a v e t h e following characteristics: 1. Be f u l l y s t e r i l e a t t h e t i m e o f i m p l a n t a t i o n a n d be n o n t o x i c . 2. Be s u r g i c a l l y c o n v e n i e n t t o i n s e r t a t o r n e a r t h e n o r m a l l o c a t i o n i n the heart. 3. Conform to the heart s t r u c t u r e r a t h e r than the heart s t r u c t u r e c o n f o r m i n g t o t h e v a l v e ( i . e . , t h e s i z e and shape of the p r o s t h e s i s should not i n t e r f e r e w i t h c a r d i a c f u n c t i o n ) .


8.

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4.

Show a m i n i m u m r e s i s t a n c e t o f l o w s o s i g n i f i c a n t pressure drop across the

5.

Have m i n i m a l r e v e r s e f l o w n e c e s s a r y f o r v a l v e c l o s u r e , so as t o keep t h e i n c o m p e t e n c e o f t h e v a l v e a t a low l e v e l . Show l o n g m e c h a n i c a l a n d s t r u c t u r a l w e a r o f t h e v a l v e . Be l o n g - l a s t i n g ( ^ 2 5 y e a r s ) , a n d m a i n t a i n i t s n o r m a l f u n c t i o n a l p e r f o r m a n c e ( i . e . , must not d e t e r i o r a t e w i t h time).

6. 7.

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YOGANATHAN ET A L .

9. 10.

as t o p r e v e n t valve.

a

Cause minimum trauma t o b l o o d e l e m e n t s and t h e e n d o t h e l i a l t i s s u e of the c a r d i o v a s c u l a r s t r u c t u r e surrounding the valve. Show a l o w p r o b a b i l i t y f o r t h r o m b o e m b o l i c c o m p l i c a t i o n s w i t h o u t t h e use o f a n t i c o a g u l a n t s . S h o u l d n o t be n o i s y a n d d i s t u r b t h e patient.

11. 12.

S h o u l d be r a d i o g r a p h i c a l l y v i s i b l e . S h o u l d have a modest p r i c e . As s t a t e d p r e v i o u s l y t h e s e r i o u s p r o b l e m s o f thromboembolism, e x c e s s t i s s u e o v e r g r o w t h , r e d - c e l l and p l a t e l e t d a m a g e , and damage to the e n d o t h e l i a l l i n i n g of the vessel wall adjacent to the valve are d i r e c t l y r e l a t e d to the f l u i d dynamics a s s o c i a t e d w i t h the various types of valve prostheses. B l a c k s h e a r and h i s c o workers (2,3) suggest that the shear s t r e s s e s required i n the b u l k o f the "flow t o hemolyze r e d b l o o d c e l l s a r e about 4 0 , 0 0 0 dynes/cm2. N e v a r i l and h i s c o - w o r k e r s (4) c o n t e n d , however, t h a t t h i s v a l u e c o u l d be a s l o w a s 1500 d y n e s / c m 2 . In v i t r o experiments (5-7) have a l s o r e c e n t l y shown t h a t p l a t e l e t s c o u l d , , be d a m a g e d b y s h e a r s t r e s s e s o f t h e o r d e r o f 1 0 0 - 5 0 0 d y n e s / c m . A formed element such as a red blood c e l l which adheres to the v e s s e l w a l l o r t o a f o r e i g n s u r f a c e ( s u c h as t h e v a l v e s u p e r s t r u c t u r e ) may be d a m a g e d b y s h e a r s t r e s s e s o f t h e o r d e r o f 10-102 dynes/cm^ ( 2 , 3 , 8 ) . L l o y d e t a l . , (9) i n d i c a t e t h a t s u b l e t h a l damage t o r e d b l o o d c e l l s c o u l d o c c u r a t s h e a r s t r e s s e s on t h e o r d e r o f 500 d y n e s / c m 2 o r l e s s . A r e c e n t s t u d y by M c l n t y r e (10) i n d i c a t e s that the red blood c e l l s of heart valve p a t i e n t s a r e more f i l t e r a b l e i n m i c r o p o r e s t h a n compared t o n o r m a l s u b j e c t s , due t o s u b l e t h a l damage t o t h e r e d c e l l s of valve r e c i p i e n t s . L e t h a l damage t o r e d b l o o d c e l l s c a u s e s hemolysis which i n turn leads to anemia. Sublethal and/or l e t h a l damage t o r e d b l o o d c e l l s c o u l d a l s o l e a d t o p l a t e l e t a d h e s i o n , a g g r e g a t i o n and c o a g u l a t i o n , r e s u l t i n g i n thrombus formation. M e c h a n i c a l damage t o p l a t e l e t s ( l e t h a l a n d s u b l e t h a l ) w i l l eventually lead to thromboembolic complications. F r y ( 1 1 , 1 2 ) has c o n d u c t e d two s t u d i e s on t h e e f f e c t s of w a l l s h e a r on t h e e n d o t h e l i a l l i n i n g o f t h e a o r t i c w a l l . He f o u n d t h a t t h e e n d o t h e l i a l c e l l s o n t h e v e s s e l w a l l c o u l d be damaged a t w a l l - s h e a r s t r e s s e s o f a b o u t 400 d y n e s / c n r and c o u l d be e r o d e d o f f t h e v e s s e l w a l l a t s h e a r s t r e s s e s o f a b o u t 950 dynes/cm2. He o b s e r v e d t h a t w h e n t h e e n d o t h e l i a l s u r f a c e w a s e x p o s e d t o s h e a r i n g s t r e s s e s a b o v e some c r i t i c a l v a l u e (400 d y n e s / c m 2 ) t h e c e l l s began t o s u f f e r s t r u c t u r a l and c h e m i c a l changes. The c r i t i c a l s t r e s s i s known as t h e " y i e l d i n g " s t r e s s .



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If a s h e a r i n g s t r e s s above the c r i t i c a l value i s a p p l i e d f o r a long time p e r i o d , the y i e l d i n g process continues u n t i l the c e l l s become m e c h a n i c a l l y u n s t a b l e and a r e washed away f r o m t h e i r m o o r i n g s t o t h e b a s e m e n t membrane i n t o t a l o r by p r o g r e s s i v e erosion of c e l l substance. As t h e e r o d e d s u r f a c e o f t h e v e s s e l w a l l i s exposed to the f l o w i n g b l o o d , d e p o s i t i o n of blood elements and t h r o m b o t i c m a t e r i a l s o c c u r . Fry found t h a t the d e p o s i t e d material consisted of fibrous t i s s u e , p l a t e l e t s , red blood c e l l s , and o t h e r u n i d e n t i f i e d d e b r i s . He s t a t e s t h a t s u c h d e p o s i t i o n could lead to intimai t h i c k e n i n g of the vessel w a l l . W o o l f and C a r s t a i r s (13) s t a t e t h a t t h e f i b r o u s t i s s u e o b s e r v e d on the a o r t i c w a l l as a r e s u l t o f i n t i a m a l t h i c k e n i n g owes i t s p r e s e n c e to e i t h e r i n f i l t r a t i o n o r thrombus f o r m a t i o n , or a combination o f t h e s e two f a c t o r s . P l a t e l e t s do n o t a d h e r e t o i n t a c t e n d o t h e l i a l c e l l s b u t t h e y do a d h e r e t o s u b e n d o t h e l i a l c o n n e c t i v e t i s s u e composed o f c o l l a g e n and o t h e r m a t e r i a l s . P l a t e l e t s , h o w e v e r , have a c c e s s to c o l l a g e n f i b e r s once the e n d o t h e l i a l l i n i n g o f a v e s s e l w a l l i s damaged o r e r o d e d o f f . The a d h e s i o n o f p l a t e l e t s t o t h e d a m a g e d v e s s e l l e a d s t o t h e s u b s e q u e n t r e l e a s e o f ADP a n d platelet factor 3 (PF-3). T h e s e s u b s t a n c e s p l a y an a c t i v e r o l e i n p l a t e l e t a g g r e g a t i o n a n d c o a g u l a t i o n , r e s p e c t i v e l y , a n d may lead to thrombus f o r m a t i o n . A red blood c e l l w i l l not s t i c k to the i n t a c t e n d o t h e l i a l l i n i n g of a vessel w a l l . If, however, the v e s s e l i n t i m a i s damaged r e s u l t i n g i n a l o s s o f e n d o t h e l i a l i n t e g r i t y , red blood c e l l s c o u l d adhere onto the v e s s e l w a l l . I f t h e adhered r e d b l o o d c e l l i s exposed t o s h e a r s on the o r d e r o f 10 t o 1 0 0 d y n e s / c m 2 i t w i l l p r o b a b l y be l e t h a l l y d a m a g e d a n d hemolyzed. R e d b l o o d c e l l s c o n t a i n ADP a n d a c l o t - p r o m o t i n g f a c t o r known a s e r y t h r o c i n . These substances are r e l e a s e d i n t o the plasma as a r e s u l t o f h e m o l y s i s , i n i t i a t i n g both p l a t e l e t a g g r e g a t i o n a n d c o a g u l a t i o n , w h i c h i n t u r n may l e a d t o thrombus formation. The m e c h a n i c a l damage t o t h e b l o o d e l e m e n t s , a s w e l l a s t o t h e e n d o t h e l i a l t i s s u e o f t h e a d j a c e n t v e s s e l w a l l , may i n a d d i t i o n t r i g g e r the complex b i o c h e m i c a l r e a c t i o n s which c o u l d l e a d t o t h e e x c e s s f i b r o u s t i s s u e o v e r g r o w t h o b s e r v e d o n some recovered heart valves. Therefore, l a r g e w a l l and b u l k turbulent s h e a r s t r e s s e s c o u l d c a u s e s e r i o u s p r o b l e m s and c o m p l i c a t i o n s in vivo. I t i s a l s o w e l l known t h a t r e g i o n s o f f l o w s t a g n a t i o n , flow s e p a r a t i o n and e x c e s s i v e l y low s h e a r , i n t h e i m m e d i a t e v i c i n i t y o f t h e v a l v e s u p e r s t r u c t u r e have been r e l a t e d t o thrombus f o r m a t i o n and/or e x c e s s t i s s u e o v e r g r o w t h on the p r o s t h e s i s . The f l o w v e l o c i t y , s h e a r s t r e s s and p r e s s u r e f i e l d s i n t h e immediate v i c i n i t y of a given heart valve p r o s t h e s i s design are d i r e c t l y r e l a t e d to the f l u i d dynamic c h a r a c t e r i s t i c s of the prosthesis. Therefore, d e t a i l e d i n v i t r o f l u i d dynamic s t u d i e s s h o u l d h e l p p r e d i c t p o t e n t i a l p r o b l e m s a n d c o m p l i c a t i o n s t h a t may a r i s e in vivo with d i f f e r e n t designs of prosthetic heart valves.


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YOGANATHAN ET A L .

115


Methodology An e x t e n s i v e s t u d y o f t h e l i t e r a t u r e was u n d e r t a k e n , and r e s u l t s f r o m o v e r 450 a r t i c l e s i n b o t h t h e m e d i c a l and e n g i n e e r i n g l i t e r a t u r e were u t i l i z e d (140. The r e s u l t s f o r t h e f o l l o w i n g heart valve prostheses are summarized i n t h i s paper: (a) StarrEdwards b a l l v a l v e s , (b) K a y - S h i l e y d i s c v a l v e , ( c ) B e a l l d i s c v a l v e , (d) B j o r k - S h i l e y t i l t i n g d i s c v a l v e , (e) Hancock p o r c i n e v a l v e , and ( f ) S t . J u d e b i - l e a f l e t v a l v e . These valve p r o s t h e s e s shown i n F i g u r e s 1 t h r o u g h 6 were c h o s e n b e c a u s e o f t h e i r p a s t and/or present p o p u l a r i t y i n c l i n i c a l use. They a l s o encompass a l l the b a s i c d e s i g n s o f v a l v e p r o s t h e s e s used d u r i n g the p a s t two d e c a d e s . In v i v o p r e s s u r e d r o p , i n v i t r o p r e s s u r e d r o p and r e g u r g i t a t i o n ( r e f l u x and l e a k a g e ) , h e m o l y s i s , and t h r o m b o e m b o l i c c o m p l i c a t i o n (TEC) d a t a were o b t a i n e d and t a b u l a t e d f o r e a c h o f the above v a l v e s . The i n v i t r o p r e s s u r e d r o p r e s u l t s w e r e o b t a i n e d i n most i n s t a n c e s from p u l s a t i l e f l o w measurements. The i n v i v o p r e s s u r e d r o p r e s u l t s p r e s e n t e d f o c u s p r i m a r i l y on p a t i e n t s who w e r e e l e c t i v e l y c a t h e t e r i z e d a n d who d i d n o t h a v e any c l i n i c a l p r o b l e m s r e l a t e d t o the p r o s t h e s i s . The r e s u l t s s h o u l d t h e r e f o r e r e f l e c t t h e i n v i v o hemodynamic p e r f o r m a n c e of normally functioning prostheses. Valve areas (VA), or otherwise known a s t h e e f f e c t i v e o r i f i c e a r e a s , w e r e c a l c u l a t e d by t h e various i n v e s t i g a t o r s from the G o r l i n or modified G o r l i n formulae (15). The i n v i v o v a l v e a r e a s g i v e a good q u a l i t a t i v e and/or q u a n t i t a t i v e r a n k i n g f o r the i n vivo pressure drop c h a r a c t e r i s t i c s of the various valves. If d i f f e r e n t valve d e s i g n s a r e s t u d i e d by t h e same i n v e s t i g a t o r s a n d / o r a t t h e same m e d i c a l c e n t e r , t h e r e s u l t s h a v e more quantitative significance. E v e n t h o u g h t h e a b s o l u t e v a l u e s o f VA may v a r y from center to center f o r a given valve d e s i g n , the r a n k i n g o f d i f f e r e n t valve types according to i n vivo valve areas are generally consistent. The m a i n r e a s o n s f o r t h e v a r i a t i o n s i n the absolute values from center to center a r e : (i) inaccuracies i n o b t a i n i n g c a r d i a c c a t h e t e r i z a t i o n d a t a ( p r e s s u r e s and f l o w s ) , ( i i ) o b t a i n i n g a s t a t i s t i c a l l y l a r g e enough p a t i e n t population and ( i i i ) d i f f e r e n t f o r m u l a e u s e d t o e s t i m a t e VA. The i n v i v o r e s u l t s do n o t c o n t a i n r e g u r g i t a t i o n d a t a b e c a u s e t h i s p a r a m e t e r c a n n o t be q u a n t i t a t i v e l y m e a s u r e d d u r i n g c a t h e t e r i z a t i o n , or other i n vivo procedures, at the present time. In were i n articles orifice

v i t r o p r e s s u r e d r o p , f l o w r a t e , and r e g u r g i t a t i o n d a t a most cases o b t a i n e d d i r e c t l y from t h e i r r e s p e c t i v e . From t h e s e d a t a t h e v a l v e a r e a s (VA) (i.e.: effective area) were c a l c u l a t e d from the f o l l o w i n g f o r m u l a : VA

(cm2)

=

^r m s 51.6



116


where 3 Q r m s = r o o t m e a n s q u a r e s y s t o l i c o r d i a s t o l i c f l o w r a t e , cm / s Δρ = m e a n s y s t o l i c o r d i a s t o l i c p r e s s u r e d r o p , mmHg In v i t r o r e g u r g i t a t i o n v o l u m e (RV) d a t a i n t h e b i o - m e d i c a l engineering literature i s generally poorly reported. O n l y RV d a t a e x p r e s s e d i n c m 3 / s t r o k e o r d a t a t h a t c o u l d be c a l c u l a t e d (from the i n f o r m a t i o n p r o v i d e d ) i n t o such a form were u s e d . In m a n y i n s t a n c e s , RV w o u l d be e x p r e s s e d i n t h e l i t e r a t u r e a s a p e r c e n t a g e , w i t h no i n f o r m a t i o n o n c a r d i a c o u t p u t a n d / o r h e a r t rate. The w o r k o f D e l l s p e r g e r e t a l . , (16) and i n o u r l a b o r a t o r y tend to i n d i c a t e that for a given v a l v e , at a f i x e d heart rate t h e v a l u e o f RV i n c n v t y s t r o k e d o e s n o t v a r y ( e x c e p t w i t h i n experimental error) with cardiac output. The i n v i t r o p r e s s u r e d r o p and r e g u r g i t a t i o n r e s u l t s g i v e a v e r y good q u a l i t a t i v e a n d / o r q u a n t i t a t i v e r a n k i n g o f t h e s t e n o t i c and r e g u r g i t a n t c h a r a c t e r i s t i c s o f t h e v a r i o u s v a l v e d e s i g n s . I f d i f f e r e n t v a l v e t y p e s w e r e s t u d i e d by t h e same i n v e s t i g a t o r t h e r e s u l t s o b t a i n e d w i l l have more q u a n t i t a t i v e importance. Even t h o u g h t h e a b s o l u t e n u m e r i c a l v a l u e s o b t a i n e d by d i f f e r e n t i n v e s t i g a t o r s may v a r y f o r a g i v e n v a l v e d e s i g n , t h e r a n k i n g o f the d i f f e r e n t valve types are g e n e r a l l y c o n s i s t e n t . The m a j o r r e a s o n s f o r t h e v a r i a t i o n s i n t h e a b s o l u t e v a l u e s among t h e d i f f e r e n t i n v e s t i g a t o r s i s because d i f f e r e n t types of pulse d u p l i c a t o r s and f l o w chamber g e o m e t r i e s have been u s e d . It s h o u l d , h o w e v e r , be n o t e d t h a t t h e r e i s b e t t e r quantitative agreement i n t h e i n v i t r o p r e s s u r e d r o p and r e g u r g i t a t i o n d a t a between d i f f e r e n t i n v e s t i g a t o r s , t h a n w i t h t h e i n v i v o hemo dynamic data from d i f f e r e n t medical c e n t e r s . Information obtained from the i n v i t r o flow v i s u a l i z a t i o n , a n d v e l o c i t y a n d s h e a r s t r e s s m e a s u r e m e n t s t u d i e s w i l l be discussed i n the t e x t . A l l t h e h e m o l y s i s and t h r o m b o e m b o l i c c o m p l i c a t i o n (TEC) t a b l e s were c o n s t r u c t e d from i n f o r m a t i o n e x t r a c t e d from t h e i r respective articles. D u r i n g t h e s t u d y i t was n o t i c e d t h a t there i s no c o n s i s t e n t s c i e n t i f i c m a n n e r i n w h i c h d a t a o n h e m o l y s i s and T E C ' s a r e r e p o r t e d i n t h e m e d i c a l l i t e r a t u r e . Elevated LDH l e v e l s , and r e d u c e d a n d / o r a b s e n t h a p t a g l o b i n l e v e l s a r e good indicators of intravascular hemolysis. Reduced h a l f - l i f e s o f r e d c e l l s and p l a t e l e t s a r e i n o u r o p i n i o n one o f t h e b e s t ways o f m o n i t o r i n g m e c h a n i c a l ( s h e a r ) damage t o b l o o d e l e m e n t s . Such t e s t s a r e i n f r e q u e n t l y done i n a c l i n i c a l e n v i r o n m e n t . Early T E C ' s and d e a t h s a r e d e f i n e d as t h o s e o c c u r r i n g d u r i n g t h e f i r s t 30 d a y s a f t e r v a l v e r e p l a c e m e n t s u r g e r y . TEC e v e n t s a r e e x p r e s s e d w h e r e p o s s i b l e a s p a t i e n t r a t i o s a n d / o r a s a r a t e (% p e r p t . yr.). B a s e d o n t h e h e m o l y s i s a n d TEC d a t a a n d o t h e r p e r t i n e n t i n f o r m a t i o n i n t h e l i t e r a t u r e , we h a v e b e e n a b l e t o d r a w c e r t a i n c o n c l u s i o n s a b o u t t h e h e m o l y t i c and t h r o m b o e m b o l i c p o t e n t i a l of the d i f f e r e n t valve designs. The l o c a t i o n s o f t h r o m b u s formation, e x c e s s t i s s u e g r o w t h a n d r e l a t e d v a l v e d y s f u n c t i o n s w i l l be discussed i n the t e x t .


8.

Results

and

(1)

Starr

Edwards

Valve

Description

Starr-Edwards

closed a

which

cloth.

occluders. January

1966.

was

1260

valve mitral

Edwards models

model

2300

aortic cloth of

orifice

cloth

of

Starr-Edwards

They were Stellite

No.

15%

21

due

for

an

also

and

model

cage

the

the

model

interface

6120

mitral

the

1200

available

orifice

in

of

the

the

valves

in

1260.

valve

6310/6320

2310

in

composite

The model

model

has

a

which

four have

track ball

metallic

closure

are

of

made

seen

struts

has

rest

of

of

fabric

valve

and

prostheses

prostheses.

supports

on

the

No.

21

cloth

covering struts

polypropylene

cloth.

multi-filament

tissue 2320/6320

discontinued.

of

models, these

These

and

problems

in

1976.

Starr-Edwards

closed single-cage struts,

aspect

of

alloy aspect

hollow

poppets, the

No. of

base 21)

the

no m e t a l - c l o t h by

were

c l o t h wear

cage

inner

except

changes

models

to

For

2310

are

hence

The

model

problems.

covered

Dacron

of

Although

(Stellite

and

wear.

models

(mitral)

inner

to

cage-struts

The

The

are

and

86% cloth

autogenous

a duplicate

6400

about

orifice

of

be m a j o r

radiographically. the

from

close.

approxi-

1970,

2320/6320

to

1968.

orifice

by

clearance.

the

cage

siliconized

was

the

area

2310/6310 were

2320 of

In

in

orifice

ball

amounts

in

could

between

ball.

problem

ball

clearance small

a

2310/6310)

the

diameter

discontinuance

alloy

supports

which

and

1968.

excessive

cloth-covered

of

(aortic)

Haynes no

metal

to

of

available

problem

continued

valve

became

prostheses.

1967

(models

the

ball-strut

the

orifice

series

increased the

the

valve from

a problem

flow

valves

against

somewhat

model

to

2400

the first

exposed seat

and models

the

in

ball

of

Starr-

cloth-covered

available

because

The

seat

metallic

were

(mitral)

Dacron

a Teflon/Polypropylene

close

in

metallic

easily

tissue

allowed

overgrowth

totally

valves

with

motion

led

the

orifice-to-ball

the

increase

Models

porous

to

by

and

design

the

purposes,

eventually

The

1968

sewing

2-percent-by-

made

(aortic)

primarily

of

reduced

with

made

tissue

was

a

are of

polypropylene

some o f

aortic

composite

introduced,

all

cage w i t h

the

durability.

seat

also

interfere were

do

comprised

and

from

6300 m i t r a l

a composite

composite It

and

comprised

formed

the

model

it

covered

autogenous

Unfortunately, of

in

c l o t h metal

from

discontinued

overgrowth

90%.

21

prostheses

are

contain

as

valve

further

The

2310/2320 evolved

of

mately

the

distinguish

valves

They were

The

No.

poppets

aortic

slightly

resemble

to

6120

radiopacity

superseded

prosthesis.

totally

which

and 1200

was

alloy

Mitral

They

cages.

The

The

to

cage

3 strut

It

6120

(TFE-fluorocarbon)

for

model

extended

6120 strut

1260

and

valves.

Stellite

Teflon

sulfate

The

Aortic

S i l a s t i c ball

polished

Model

barium

Valves

1200/1260

combines

The

weight

cloth

Ball

single-cage

radio-opaque

ring


Discussion

Ta] The

117


YOGANATHAN E T AL.

and ring

and

contact.

tubular-knitted

orifice

cloth

is

thread

which

together

made

are

cage

from with



118


Figure

1.

(a) (b)

Starr-Edwards Starr-Edwards

ball ball

valve, valve,

model model

1260 6120


8.

YOGANATHAN ET A L .


119


the exposed m e t a l l i c supports produces a composite s e a t i n g surface which the b a l l impacts at c l o s u r e . The s e w i n g r i n g i s made o f T e f l o n a n d p o l y p r o p y l e n e c l o t h o v e r a s i l i c o n e f o a m padding. The model 2400 v a l v e has 3 - s t r u t c a g e w h i l e t h e model 6400 cage has 4 s t r u t s , (b) JTn V i v o R e s u l t s The S t a r r - E d w a r d s a o r t i c b a l l v a l v e p r o s t h e s e s had v a l v e a r e a s ( V A ' s ) o f 0 . 9 2 t o 1 . 9 c m 2 , f o r v a l v e s i z e s o f 21 t o 2 9 mm. For t h e m i t r a l p r o s t h e s e s i n t h e s i z e r a n g e o f 2 6 t o 3 4 mm, V A 1 s w e r e i n the range of 1.4 to 2.7 cm2. These v a l u e s are s i m i l a r t o t h o s e o b s e r v e d w i t h o t h e r b a l l v a l v e p r o s t h e s e s , s u c h as t h e Smeloff valve design. T h e r e a r e numerous a r t i c l e s on t h e h e m o l y s i s and t h r o m b o e m b o l i c c o m p l i c a t i o n s c r e a t e d by t h e d i f f e r e n t d e s i g n s o f Starr-Edwards ball valves. The r e s u l t s i n d i c a t e w i t h o u t a doubt that the c o m p l e t e l y c l o t h covered s t r u t models 2300, 2310, 2 3 2 0 , 6 3 0 0 , 6 3 1 0 a n d 6 3 2 0 c a u s e d m o d e r a t e a n d i n many c a s e s severe hemolysis (17-22). The m o d e l s 2400 and 6400 t e n d t o cause l e s s h e m o l y s i s compared to the o t h e r c l o t h covered StarrEdwards b a l l v a l v e s ( 1 8 , 2 3 - 2 5 ) . The m o d e l s 1 2 0 0 / 1 2 6 0 and 6120 n o n - c l o t h covered valves cause m i l d to moderate h e m o l y s i s . The t h r o m b o e m b o l i c c o m p l i c a t i o n s seem t o be g r e a t e r w i t h t h e n o n c l o t h c o v e r e d models ( 1 2 0 0 , 1 2 6 0 , 6 0 0 0 , 6120) compared t o t h e c l o t h covered models (2300, 2310, 2320, 2400, 6300, 6310, 6320, 6400). This fact i s substantiated i n c l i n i c a l studies conducted o n b o t h c l o t h a n d n o n - c l o t h c o v e r e d m o d e l s by t h e same g r o u p o f researchers (18,26-30). A c c o r d i n g t o L e f r a k and S t a r r ( 3 1 J , the c l o t h c o v e r e d v a l v e s have an e m b o l u s f r e e r a t e o f 95% a t 3 y e a r s v e r s u s 81% f o r t h e n o n - c l o t h c o v e r e d p r o s t h e s e s . The TEC rates for the Starr-Edwards b a l l v a l v e s s e e m t o be i n t h e r a n g e o f 3 t o 6 . 5 % p e r p t . y r . w i t h a n t i c o a g u l a t i o n t h e r a p y a n d a s h i g h a s 10% per pt. y r . without a n t i c o a g u l a t i o n therapy. The c l o t h c o v e r e d Starr-Edwards b a l l v a l v e s w e r e d e v e l o p e d i n an a t t e m p t t o r e d u c e t h r o m b o e m b o l i c c o m p l i c a t i o n s by e n c o u r a g i n g a t h i n l a y e r o f e n d o t h e l i a l i z a t i o n on the c l o t h c o v e r i n g . The c l o t h c o v e r e d v a l v e s , h o w e v e r , do r e q u i r e a n t i c o a g u l a t i o n t h e r a p y . T h i s was determined q u i t e c o n c l u s i v e l y from c l i n i c a l s t u d i e s where a n t i c o a g u l a t i o n t h e r a p y was n o t u s e d ( 1 8 , 3 2 , 3 3 , 3 4 ) . Thrombus f o r m a t i o n and t i s s u e o v e r g r o w t h on v a r i o u s p a r t s of the super s t r u c t u r e of the Starr-Edwards ball valves i s well documented ( 1 9 , 3 1 - 3 8 ) . R o b e r t s and h i s c o - w o r k e r s (18,35-37) g i v e d e t a i l e d p a t h o l o g i c d e s c r i p t i o n s o f the thrombus formation and t i s s u e o v e r g r o w t h o b s e r v e d on S t a r r - E d w a r d s ball valves. The examinations of recovered Starr-Edwards a o r t i c and m i t r a l ball v a l v e s have shown: ( i ) thrombus f o r m a t i o n a t the apex o f the c a g e , at t h e base o f t h e t h r e e s t r u t s and i n v a r y i n g degrees a l o n g t h e s t r u t s , and ( i i ) e x c e s s t i s s u e g r o w t h on t h e downstream s i d e o f the s e w i n g r i n g on a l l m o d e l s , a l o n g t h e s t r u t s (inside and o u t s i d e ) and a l o n g t h e f a b r i c on t h e i n s i d e s u r f a c e o f t h e



120


o r i f i c e of the c l o t h covered models. Thrombus has a l s o been observed on the i n f l o w s u r f a c e o f the o r i f i c e r i n g . S t u d i e s by R o b e r t s and h i s c o - w o r k e r s ( 1 , 1 9 , 3 5 - 3 7 ) have a l s o o b s e r v e d e n d o t h e l i a l damage a n d t i s s u e p r o l i f e r a t i o n o f t h e p r o x i m a l ascending aorta i n patients with a o r t i c prostheses. They have found i n t i m a i t h i c k e n i n g o f t h e a o r t i c r o o t including the area of the coronary a r t e r i a l o s t i a . The t h i c k e n i n g was p r o d u c e d by t h e d e p o s i t i o n o f f i b r o u s t i s s u e o n t h e i n t e r n a l e l a s t i c membrane o f t h e p r o x i m a l a s c e n d i n g a o r t a . The d e g r e e o f i n t i m a i p r o l i f e r a t i o n v a r i e d from minimal to extremely severe. I n some c a s e s t h e i n t i m a i t h i c k e n i n g i n v o l v e d n o t o n l y t h e ascending aorta but a l s o the proximal coronary a r t e r i e s . Roberts (1_) s t a t e s t h a t i n t i m a i f i b r o s i s i n t h e a o r t i c r o o t may b e a p r e v i o u s l y unrecognized consequence o f a o r t i c valve replacement, and i s a p o t e n t i a l p r o b l e m w i t h a l l p e r i p h e r a l f l o w t y p e a o r t i c prostheses. The c o m b i n a t i o n o f t h r o m b u s f o r m a t i o n and f i b r o u s t i s s u e o v e r g r o w t h c a n be a l e t h a l c o m b i n a t i o n , a s h a s b e e n l e a r n e d f r o m the recovered Starr-Edwards ball valves. The i d e a o f g r o w i n g a t h i n layer of neo-intima along the f a b r i c of the c l o t h covered valves d i d not uniformly succeed. With a l l the c l o t h covered models ( 2 3 0 0 - 1 0 - 2 0 , 2400, 6 3 0 0 - 1 0 - 2 0 , 6 4 0 0 ) , t i s s u e overgrowth o c c u r r e d on t h e f a b r i c w h i c h l i n e d t h e o r i f i c e and a t t i m e s c a u s e d t h e v a l v e s t o become s t e n o t i c . In a d d i t i o n , t h e models w i t h the completely f a b r i c covered cages (2300-10-20, 6300-10-20), c o u l d develop e x c e s s i v e f i b r o u s t i s s u e and thrombus growth on the inner aspects of the s t r u t s which could i n turn cause: e i t h e r ( i ) t h e p o p p e t t o s t i c k i n an open p o s i t i o n , o r ( i i ) a reduction i n the opening excursion of the poppet. If the stuck p o p p e t phenomena was n o t d i a g n o s e d i m m e d i a t e l y t h e c o n s e q u e n c e s were g e n e r a l l y f a t a l . The 2 3 0 0 - 1 0 - 2 0 and 6 3 0 0 - 1 0 - 2 0 models a l s o had v a r y i n g d e g r e e s o f c l o t h w e a r due t o a b r a s i o n between t h e metal poppet and t h e f a b r i c . C l o t h wear w i t h these p r o s t h e s e s often l e d to severe hemolytic anemia. The models 2400 and 6400 do n o t seem t o s u f f e r f r o m t h e p r o b l e m o f c l o t h w e a r a n d t h a t i s p r o b a b l y one o f t h e r e a s o n s why t h e y c a u s e l e s s h e m o l y s i s comp a r e d t o t h e 2300 and 6300 s e r i e s . T h e y d o , h o w e v e r , seem t o c a u s e more h e m o l y s i s compared t o t h e n o n - c l o t h c o v e r e d (1200/1260, 6120) p r o s t h e s e s . The f a c t t h a t t h e c l o t h c o v e r e d m o d e l s c a u s e d more h e m o l y s i s compared t o t h e n o n - c l o t h c o v e r e d models i s h i g h l i g h t e d im s t u d i e s where b o t h t y p e s o f v a l v e s were investigated (17-25). Hamby e t a l . , ( 3 9 ) i n a n e x c e l l e n t c l i n i c a l study, demonstrated the hydrodynamic i n s t a b i l i t y o f the Starr-Edwards a o r t i c b a l l v a l v e s i n 41 p a t i e n t s . The s t u d y combined c i n e f l u o r s c o p y , p h o n o c a r d i o g r a p h y and hemodynamic measurements. In 20 o f t h e p a t i e n t s t h e poppet r e m a i n e d i n a r e l a t i v e l y f i x e d p o s i t i o n (even though i t r o t a t e d ) a t t h e apex o f t h e cage d u r i n g systolic ejection. I n 11 p a t i e n t s t h e p o p p e t b o u n c e d a w a y f r o m the apex o f t h e cage d u r i n g e a r l y e j e c t i o n and p r o m p t l y returned


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t o the apex d u r i n g the r e m a i n d e r o f the e j e c t i o n p e r i o d . I n 10 p a t i e n t s p r e m a t u r e p a r t i a l c l o s u r e o f t h e v a l v e was o b s e r v e d during ejection. A f t e r s t r i k i n g the apex o f the cage d u r i n g e a r l y e j e c t i o n the poppet descended almost h a l f the d i s t a n c e t o w a r d t h e base o f t h e v a l v e and r e m a i n e d i n a r e l a t i v e l y f i x e d , p a r t i a l l y closed p o s i t i o n during the remainder of the e j e c t i o n period. I n s t a b i l i t y of the poppets of the Starr-Edwards ball v a l v e s h a s a l s o b e e n o b s e r v e d i n some o f o u r p a t i e n t s a t t h e USC-LA County M e d i c a l C e n t e r . (c)

In

Vitro

Results

The i n v i t r o p r e s s u r e d r o p s t u d i e s i n d i c a t e c a l c u l a t e d V A ' s of 1 . 0 4 t o 2 . 1 2 c m 2 f o r a o r t i c a n d m i t r a l v a l v e s i n t h e 19 t o 3 2 mm size range. A s s t a t e d b y L e f r a k a n d S t a r r ( 3 1 ) t h e r e i s no d i f f e r e n c e i n t h e i n v i t r o p r e s s u r e d r o p and r e g u r g i t a n t c h a r a c t e r i s t i c s o f the n o n - c l o t h c o v e r e d (1200/1260, 6120) and t h e c l o t h c o v e r e d (2310/2320, 2400, 6 3 1 0 / 2 0 , 6400) p r o s t h e s e s . The i n v i t r o r e s u l t s a l s o i n d i c a t e l o w r e g u r g i t a n t v o l u m e s ( ^ 6 cm^/beat or l e s s ) , f o r the Starr-Edwards ball valves. The S t a r r - E d w a r d s b a l l v a l v e s h a v e no l e a k a g e b a c k f l o w . T h e r e have been a number o f f l o w v i s u a l i z a t i o n s t u d i e s c o n d u c t e d on t h e S t a r r - E d w a r d s b a l l v a l v e s i n the a o r t i c and mitral positions (40-44). W i e t i n g (44J o b s e r v e d the f l o w p a t t e r n s d o w n s t r e a m f r o m a 27 mm m o d e l 1 2 6 0 b a l l v a l v e , under pulsatile flow conditions. D u r i n g s y s t o l e he o b s e r v e d a l a r g e t u r b u l e n t wake d i s t a l t o t h e b a l l . He a l s o f o u n d t h a t t h e b a l l bounced a t t h e apex o f t h e cage and t h i s p r o b a b l y i n c r e a s e d s i z e of the t u r b u l e n t wake. The l a r g e a m p l i t u d e b o u n c e s i n c r e a s e d t h e r e l a t i v e v e l o c i t y between t h e s u r f a c e o f t h e b a l l and t h e f l u i d flowing past i t . Yoganathan e t a l . , ( 4 5 , 4 6 ) and F i g l i o l a (47) have a l s o o b s e r v e d t h e p o p p e t i n s t a b i l i t y phenomena w i t h t h e model 1260 valve. As o b s e r v e d by Y o g a n a t h a n e t a l . , i n t h e i r s t u d i e s t h e i n s t a b i l i t y of the poppet leads to l a r g e r pressure drops a c r o s s the p r o s t h e s i s . D e l l s p e r g e r and W i e t i n g (48) s t u d i e d a model 6400 v a l v e . In t h e m i t r a l p o s i t i o n t h e y o b s e r v e d boundary l a y e r s e p a r a t i o n r e s u l t i n g i n a s t a g n a t i o n p o i n t at t h e apex and a t o r o i d a l v o r t e x downstream from the v a l v e d u r i n g most o f diastole. S m e l o f f e t a l . , (40) under p u l s a t i l e f l o w o b s e r v e d an a r e a o f s t a s i s a t t h e apex o f t h e cage and a r e g i o n o f f l o w separation adjacent to the sewing r i n g . W r i g h t and Temple s t u d i e d f l o w p a t t e r n s a r o u n d a 2 4 mm a o r t i c ( m o d e l 2 4 0 0 ) a n d a 3 2 mm m i t r a l ( m o d e l 6 4 0 0 ) v a l v e s u n d e r p u l s a t i l e f l o w c o n d i t i o n s . In t h e a o r t i c p o s i t i o n t h e y o b s e r v e d a s m a l l d i s t u r b a n c e e x t e n d i n g about h a l f the b a l l d i a m e t e r i m m e d i a t e l y downstream from the apex of the cage. This region of flow gradually extended throughout s y s t o l e u n t i l a f t e r 2 5 0 ms ( 5 / 6 o f t h e w a y t h r o u g h s y s t o l e ) it was a b o u t 1 . 5 b a l l d i a m e t e r s i n l e n g t h . In t h e m i t r a l p o s i t i o n t h e y o b s e r v e d an a n n u l a r v o r t e x ( c a u s e d by f l o w s e p a r a t i o n ) in the v e n t r i c l e so t h a t f l o w o c c u r r e d r e t r o g r a d e l y towards the r e a r


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o f t h e cage and p o p p e t . Flow i n f l o w chamber w a l l and t h e p o p p e t

the a n n u l a r r e g i o n between s u r f a c e was j e t like.

the

T i l l m a n n (49) has measured t h e " w a l l " ( i . e . s u r f a c e ) s h e a r stress along the i n s i d e of the o r i f i c e during s y s t o l e , using h o t - f i l m shear probes. He m e a s u r e d a m a x i m u m a v e r a g e s h e a r s t r e s s o f 850 d y n e s / c m 2 and a p e a k s h e a r s t r e s s o f 1800 d y n e s / c m 2 . The maximum v a l u e s o c c u r r e d a t p e a k s y s t o l e . In a r e c e n t s t u d y P h i l l i p s e t a l . , made v e l o c i t y m e a s u r e m e n t s d o w n s t r e a m f r o m a 2 7 mm m o d e l ( 1 2 6 0 v a l v e ) u n d e r p u l s a t i l e f l o w c o n d i t i o n s . M e a s u r e m e n t s w e r e made 2 5 mm ( a b o u t 5 mm d o w n s t r e a m f r o m t h e c a g e a p e x ) , a n d 3 0 mm d o w n s t r e a m f r o m t h e v a l v e . They observed a l a r g e t u r b u l e n t wake i n t h i s r e g i o n . Peak v e l o c i t i e s o f about 350 cm/s w e r e m e a s u r e d n e a r t h e w a l l s o f t h e f l o w c h a n n e l a t p e a k s y s t o l e ( p e a k f l o w o f a b o u t 45 1 / m i n ) . The f l o w n e a r t h e w a l l s was j e t l i k e . RMS a x i a l v e l o c i t i e s o n t h e o r d e r o f 1 2 5 c m / s were a l s o measured. Average t u r b u l e n t shear s t r e s s e s d u r i n g p e a k f l o w w e r e e s t i m a t e d t o be o n t h e o r d e r o f 3 0 0 0 d y n e s / c m 2 . I t i s e x p e c t e d t h a t l a r g e r t u r b u l e n t s h e a r s t r e s s e s w o u l d be observed closer to the valve. F i g l i o l a has measured v e l o c i t y and s h e a r s t r e s s e s downstream f r o m a 2 5 mm ( m o d e l 1 2 6 0 ) a o r t i c v a l v e a t a s t e a d y f l o w r a t e o f 25 1/min ( 4 7 ) . He o b s e r v e d r e g i o n s o f s e p a r a t e d f l o w i n t h e s i n u s r e g i o n a t t a c h e d to the sewing r i n g , along the cage s t r u t s , and d o w n s t r e a m f r o m t h e p o p p e t . Maximum w a l l s h e a r s t r e s s e s o n t h e o r d e r o f 500 t o 850 d y n e s / c m 2 were m e a s u r e d . Turbulence i n t e n s i t i e s a s h i g h a s 40% and b u l k t u r b u l e n t s h e a r s t r e s s e s o f a b o u t 6 0 0 d y n e s / c m 2 ( m a x i m u m v a l u e ) w e r e m e a s u r e d 2 2 mm d o w n s t r e a m ( a b o u t 4 mm d o w n s t r e a m f r o m c a g e a p e x ) f r o m t h e v a l v e . He a l s o was a b l e t o m e a s u r e a maximum o c c l u d e r w a l l s h e a r s t r e s s o f 3210 d y n e s / c m 2 . F i g l i o l a a l s o made v e l o c i t y a n d s h e a r m e a s u r e m e n t s d o w n s t r e a m o f a m o d e l 2 3 2 0 v a l v e ( 2 5 mm v a l v e s i z e ) a t a s t e a d y f l o w r a t e o f 25 1 / m i n . The v e l o c i t y m e a s u r e m e n t s r e v e a l e d regions of separated flow i n the sinus attached to the sewing r i n g , d i s t a l t o t h e b a l l , and a l o n g t h e cage s t r u t s , s i m i l a r t o t h o s e o b s e r v e d w i t h t h e model 1260 v a l v e . The maximum w a l l s h e a r s t r e s s m e a s u r e d was o n t h e o r d e r o f 1300 d y n e s / c m 2 . Turbulence i n t e n s i t i e s as h i g h as 40% and t u r b u l e n c e s h e a r s t r e s s e s as l a r g e a s 711 d y n e s / c m 2 w e r e m e a s u r e d 2 2 . 5 mm d o w n s t r e a m f r o m t h e v a l v e . O c c l u d e r w a l l s h e a r s t r e s s e s were on t h e o r d e r o f 2300 d y n e s / c m 2 . F i g l i o l a s t a t e s t h a t the s m a l l e r values of w a l l shear measured w i t h t h e model 1260 v a l v e as o p p o s e d t o t h e model 2320 v a l v e can be a t t r i b u t e d t o t h e s h o r t e r p r o f i l e o f t h e m o d e l 1260 v a l v e (47). The s h o r t e r p r o f i l e e n a b l e s t h e e n t i r e o c c l u d e r t o be p o s i t i o n e d w i t h i n the sinus r e g i o n . T h e r e f o r e , t h e b l o c k a g e due t o t h e o c c l u d e r i s l e s s as t h e c r o s s - s e c t i o n a l a r e a i s l a r g e r w i t h i n the sinus r e g i o n . Y o g a n a t h a n e t a l . , h a v e a l s o made v e l o c i t y a n d s h e a r s t r e s s m e a s u r e m e n t s d o w n s t r e a m f r o m a 2 7 mm ( m o d e l 1260) v a l v e i n an a o r t i c chamber under s t e a d y f l o w c o n d i t i o n s ( 4 5 , 4 6 ) . Experiments w e r e c o n d u c t e d a t s t e a d y f l o w r a t e s o f 10 a n d 2 5 1 / m i n . They



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have i d e n t i f i e d a r e g i o n o f s t a s i s a t t h e apex o f t h e c a g e , and a r e g i o n o f f l o w s e p a r a t i o n w h i c h was a t t a c h e d t o t h e a o r t i c s i d e o f t h e sewing r i n g and t h e base o f t h e t h r e e s t r u t s and extended a b o u t 2 t o 5 mm d o w n s t r e a m f r o m t h e v a l v e a l o n g t h e w a l l s o f the flow chamber. At a f l o w r a t e o f 25 1/min t h e r e g i o n o f s t a s i s w a s a b o u t 7 t o 8 mm i n s i z e . Maximum w a l l s h e a r s m e a s u r e d were o n t h e o r d e r o f 1750 d y n e s / c m 2 , and p o p p e t w a l l s h e a r s were on t h e o r d e r o f 2500 t o 2800 d y n e s / c m 2 . Turbulence i n t e n s i t y l e v e l s a s h i g h as 50% were m e a s u r e d i n t h e wake r e g i o n i m m e d i a t e l y downstream from t h e p o p p e t , and i n t h e a n n u l a r r e g i o n between t h e poppet s u r f a c e . Maximum turbulent s h e a r s t r e s s e s on t h e o r d e r o f 2000 t o 5000 d y n e s / c m 2 (peak v a l u e s ) were measured i n t h e s e r e g i o n s , (d) Correlation The i n v i v o a n d i n v i t r o p r e s s u r e m e a s u r e m e n t s i n d i c a t e t h a t like o t h e r b a l l v a l v e s , due t o i t s c e n t r a l l y o c c l u d i n g d e s i g n , t h e Starr-Edwards b a l l v a l v e s a r e m o d e r a t e l y s t e n o t i c i n t h e medium to larger s i z e s . In the s m a l l e r s i z e s the v a l v e s a r e very stenotic. P a t i e n t s w i t h t h i s p r o s t h e s i s w o u l d n o t be a b l e t o lead very strenuous l i f e s t y l e s . The p r o s t h e s i s does have l o w r e g u r g i t a n t v o l u m e s , t h e l o w e s t among m e c h a n i c a l p r o s t h e s e s i n current clinical use. The i n v i v o and i n v i t r o d a t a seem t o indicate that the i n s t a b i l i t y of the s i l i c o n e rubber poppet (1200/1260, 6120) c o u l d lead t o l a r g e r pressure drops a c r o s s the prosthesis. The l a r g e w a l l s h e a r s t r e s s e s c r e a t e d by t h e Starr-Edwards b a l l v a l v e s c o u l d c a u s e l e t h a l damage t o t h e e n d o t h e l i a l lining of the vessel wall adjacent to the valve, e s p e c i a l l y i n the aortic position. The b u l k t u r b u l e n t s h e a r s t r e s s e s a r e l a r g e enough t o c a u s e s u b l e t h a l a n d / o r l e t h a l damage t o t h e r e d c e l l s and p l a t e l e t s . Damage t o t h e r e d c e l l s a n d p l a t e l e t s w i l l reduce t h e i r h a l f - l i f e s , as w e l l as cause hemolysis and thromboembolic complications. The s h e a r s t r e s s e s i m m e d i a t e l y a d j a c e n t t o t h e v a l v e cage ( i n t h e a n n u l a r r e g i o n ) a r e l a r g e enough t o l e t h a l l y damage a n y f o r m e d e l e m e n t s o f b l o o d w h i c h may a d h e r e t o t h e v a l v e cage o r poppet. The c l i n i c a l d a t a ( 1 7 , 1 8 - 2 5 ) i n d i c a t e very c l e a r l y t h a t t h e c l o t h covered models (2300-10-20, 2400, 6 3 0 0 - 1 0 - 2 0 , 6400) c r e a t e more h e m o l y s i s t h a n t h e n o n - c l o t h covered models (1200/1260, 6120). The most p r o b a b l e and l o g i c a l e x p l a n a t i o n f o r t h i s c l i n i c a l o b s e r v a t i o n i s that the porous c l o t h c o v e r i n g , w h i c h i s r o u g h , p r o v i d e s an i d e a l f o r e i g n s u r f a c e f o r t h e adhesion o f t h e r e d c e l l s as they f l o w past t h e v a l v e struts. Once a d h e r e d , t h e r e d c e l l s undergo s h e a r s t r e s s e s o n the order o f 1 0 2 - 1 0 3 dynes/cm2 which lead to t h e i r d e s t r u c t i o n and c a u s e h e m o l y s i s . The r e g i o n s o f s t a s i s a t t h e c a g e a p e x a n d f l o w s e p a r a t i o n immediately downstream from the b a l l c o u l d l e a d t o thrombus formation at the apex. The r e g i o n o f f l o w s e p a r a t i o n a t t h e base o f t h e t h r e e s t r u t s and a l o n g them c o u l d e n c o u r a g e thrombotic m a t e r i a l t o f o r m a t t h e base and t h e n grow a l o n g t h e s t r u t s . The



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r e g i o n o f s e p a r a t i o n attached t o the downstream s i d e o f the sewing r i n g could lead to the excess growth o f f i b r o u s t i s s u e on t h a t p o r t i o n o f t h e s e w i n g r i n g . In a d d i t i o n , the flow separation along the s t r u t s of the completely c l o t h covered strut valves (2300-10-20, 6300-10-20) could encourage the growth o f excess t i s s u e , e s p e c i a l l y along the inner aspects, since the f l o w and shear a r e low i n t h o s e l o c a t i o n s . The f i b r o u s t i s s u e overgrowth problem observed with the completely f a b r i c covered s t r u t p r o s t h e s e s has m a i n l y o c c u r r e d on t h e i n n e r a s p e c t s o f the cage. The c l o t h c o v e r i n g a l o n g t h e i n s i d e o f t h e o r i f i c e p r o b a b l y a l s o causes f l o w s e p a r a t i o n , and i f so c o u l d l e a d t o e x c e s s t i s s u e growth a l o n g t h e f a b r i c i n t h e o r i f i c e and c a u s e t h e v a l v e t o become s t e n o t i c , a s o b s e r v e d clinically.

(2) Jà)

Kay-Shiley Valve

Disc

Valve

Description

The f i r s t K a y - S h i l e y M i t r a l v a l v e was i m p l a n t e d i n 1965 a n d underwent d e s i g n and m a t e r i a l changes u n t i l t h e f i n a l muscle guard s e r i e s i n 1969. T h e f i r s t ( s e r i e s K) v a l v e c o n s i s t e d o f a S i l i c o n e d i s c held i n a S t e l l i t e metal cage. The amount o f c l o t h c o v e r i n g was l a t e r i n c r e a s e d i n an a t t e m p t t o d e c r e a s e t h e p o t e n t i a l f o r thromboembolism ( s e r i e s T ) . The m a j o r d e s i g n c h a n g e made t h e r e a f t e r w a s d e v e l o p m e n t o f t h e m u s c l e g u a r d t o prevent i n f r i n g e m e n t o f the v e n t r i c u l a r muscle on the v a l v e . The m u s c l e g u a r d s e r i e s MG a n d TG (MG = M i t r a l G u a r d s a n d TG = T r i c u s p i d Guards) were i n t r o d u c e d i n 1968 and t h e e x t e n t o f c l o t h c o v e r i n g was i n c r e a s e d i n 1969 (MGC, T G C ) . The l a s t m o d i f i c a t i o n was c h a n g i n g t h e d i s c f r o m S i l i c o n e t o D e l r i n (MGCD, T G C D ) . (b) In V i v o R e s u l t s 9 The K a y - S h i l e y m i t r a l v a l v e had c a l c u l a t e d V A ' s o f 0 . 9 t o 2 . 1 c n r i n t h e 2 8 t o 3 3 mm s i z e r a n g e . These r e s u l t s i n d i c a t e t h i s p r o s t h e s i s i s more s t e n o t i c t h a n t h e c a g e d b a l l t y p e v a l v e s . Our s t u d y i n d i c a t e s t h e r e a r e v e r y few a r t i c l e s on h e m o l y s i s w i t h the Kay-Shiley valve. The v a l v e d i d n o t seem t o c a u s e c l i n i c a l l y s i g n i f i c a n t h e m o l y s i s , but probably caused m i l d hemolysis. One of the major problems w i t h t h i s p r o s t h e s i s was, however, thromboembolic complications. TEC r a t e s a s h i g h as 3 4 . 4 % p e r p t . y r . have been o b s e r v e d w i t h t h i s p r o s t h e s i s ( 5 2 ) . Thrombus f o r m a t i o n on t h e v a l v e s u p e r s t r u c t u r e c a u s i n g d y s f u n c t i o n s o f t h e K a y - S h i l e y v a l v e i s w e l l documented i n the l i t e r a t u r e (1,19,35,51-55,57). Thrombi were m a i n l y l o c a t e d a t t h e j u n c t i o n o f t h e c a g e s t r u t s w i t h t h e m e t a l o r i f i c e r i n g , up t h e v e r t i c a l s t r u t s f o r v a r i a b l e d i s t a n c e s , and o c c a s i o n a l l y c o m p l e t e l y c o v e r i n g the e n t i r e metal s u p e r s t r u c t u r e . C l o t s have a l s o been o b s e r v e d on t h e d i s c and on t h e sewing r i n g . The p r o s t h e s i s has o c c a s i o n a l l y been c o m p l e t e l y o c c l u d e d by t h r o m b o t i c m a t e r i a l . Excess t i s s u e growth on the sewing r i n g problem with t h i s prosthesis (38,55-58). In movement o f t h e d i s c was s e v e r e l y r e s t r i c t e d overgrowth between the d i s c and sewing r i n g .

has a l s o been a some c a s e s t h e because o f t i s s u e In o t h e r cases



8.

YOGANATHAN ET A L .


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p a r t o f t h e d i s c has been t r a p p e d by t i s s u e o v e r g r o w t h and thrombus f o r m a t i o n . Such e n t r a p m e n t has t r a n s f o r m e d t h e d i s c i n t o a hinged mechanism, t h e r e b y r e d u c i n g the f l o w o r i f i c e , as w e l l as l e a d i n g t o a c c e l e r a t e d edge w e a r o f t h e d i s c by t h e m e t a l struts (31). E x c e s s t i s s u e g r o w t h a l o n g t h e s e w i n g r i n g have on o c c a s i o n s i m p a i r e d t h e r o t a t i o n o f t h e d i s c . This impairment has l e d t o g r o o v i n g o f t h e downstream f a c e o f t h e d i s c f r o m mechanical contact with the horizontal struts (31,38,57). (c) In V i t r o R e s u l t s Very few i n v i t r o s t u d i e s e x i s t on t h e K a y - S h i l e y v a l v e . The l i m i t e d i n v i t r o pressure drop s t u d i e s i n d i c a t e VA's of about 1 . 9 0 c m ^ T o r t h e s i z e 31 mm v a l v e s i n t h e m i t r a l p o s i t i o n . Wei t i n g h a s o b s e r v e d t h e f l o w p a t t e r n s a r o u n d a 2 8 mm K a y - S h i l e y v a l v e i n an a o r t i c chamber ( 4 4 ) . He o b s e r v e d a s y m m e t r i c a l t o r o i d a l v o r t e x and a wake d o w n s t r e a m f r o m t h e d i s c c a u s e d by boundary l a y e r s e p a r a t i o n d u r i n g s y s t o l e . He a l s o o b s e r v e d a n area of s t a s i s at the center of the d i s t a l surface of the d i s c . The f l o w was j e t l i k e i n t h e r e g i o n s b e t w e e n t h e d i s c a n d t h e flow channel w a l l s . S i m i l a r f l o w v i s u a l i z a t i o n s t u d i e s and o b s e r v a t i o n s h a v e b e e n made b y D u f f ( 5 9 ) . F i g l i o l a (47J has made v e l o c i t y a n d s h e a r s t r e s s m e a s u r e m e n t s d o w n s t r e a m f r o m a 2 7 mm K a y - S h i l e y v a l v e (T s e r i e s ) i n a n a o r t i c c h a m b e r u n d e r steady flow conditions. He o b s e r v e d a j e t t y p e f l o w b e t w e e n t h e poppet and f l o w chamber w a l l . He a l s o o b s e r v e d f l o w s e p a r a t i o n a t t h e sewing r i n g , and a t t h e j u n c t i o n of the v e r t i c a l struts and t h e o r i f i c e r i n g . A l a r g e wake w i t h r e c i r c u l a t i n g f l o w was m o n i t o r e d d o w n s t r e a m f r o m t h e f a c e o f t h e d i s c . At a f l o w r a t e o f 2 5 1 / m i n he m e a s u r e d a m a x i m u m w a l l s h e a r s t r e s s o f 2 5 4 8 d y n e s / c m 2 , t u r b u l e n c e i n t e n s i t i e s o f 48% a n d R e y n o l d s s h e a r s t r e s s e s o f 800 dynes/cm2. He a l s o w a s a b l e t o m e a s u r e s h e a r s t r e s s o f a b o u t 775 d y n e s / c m 2 a t t h e o c c l u d e r w a l l s u r f a c e . The R e y n o l d s s t r e s s w a s m e a s u r e d a b o u t 2 5 mm d o w n s t r e a m f r o m t h e valve. F i g l i o l a s t a t e s t h a t even l a r g e r values o f Reynolds shear s t r e s s could occur c l o s e r to the valve o c c l u d e r . Yoganathan e t a l . , ( 4 5 , 6 0 , 6 1 ) conducted v e l o c i t y measurements d o w n s t r e a m o f a 2 6 mm S t a r r - E d w a r d s d i s c v a l v e i n a n a o r t i c chamber. The S t a r r - E d w a r d s d i s c v a l v e i s q u i t e s i m i l a r t o t h e Kay-Shiley valve. A l a r g e r e g i o n o f f l o w s t a g n a t i o n 2 0 mm w i d e was o b s e r v e d a c r o s s t h e f a c e o f t h e d i s c . At a flow rate o f 25 1/min a maximum w a l l s h e a r s t r e s s o f 3200 d y n e s / c m 2 , a n d t u r b u l e n t i n t e n s i t i e s o f 50% were m e a s u r e d . Turbulent shear s t r e s s e s on t h e o r d e r o f 2000 t o 5000 d y n e s / c m 2 were e s t i m a t e d . P r e s s u r e drop measurements (45) a c r o s s t h i s v a l v e i n d i c a t e d i t was t h e m o s t s t e n o t i c m e c h a n i c a l v a l v e d e s i g n ( i . e . : disc type valve). (d) Correlation The l i m i t e d i n v i v o and t h e v e r y l i m i t e d i n v i t r o p r e s s u r e d r o p results available for the Kay-Shiley disc valve indicate that i t i s more s t e n o t i c t h a n t h e b a l l t y p e v a l v e s . As s t a t e d by



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R o b e r t s (1_) t h e d i s c t y p e v a l v e s a r e t h e l e a s t d e s i r a b l e p r o s t h e t i c c a r d i a c v a l v e s now i n u s e . They are a l s o the most obstructive. The w a l l s h e a r s t r e s s e s c r e a t e d by t h i s t y p e o f v a l v e c o u l d e a s i l y damage t h e e n d o t h e l i a l l i n i n g o f t h e v e s s e l w a l l s adjacent to the p r o s t h e s i s . The t u r b u l e n t s h e a r s t r e s s e s c o u l d c a u s e s u b l e t h a l a n d / o r l e t h a l damage t o r e d c e l l s and platelets. S u c h b l o o d e l e m e n t damage c o u l d c l i n i c a l l y c a u s e h e m o l y t i c and t h r o m b o e m b o l i c p r o b l e m s . The r e g i o n o f s t a s i s across the face of the d i s c could encourage thrombotic m a t e r i a l t o f o r m t h e r e as has been o b s e r v e d w i t h r e c o v e r e d v a l v e s . The regions of flow separation at the j u n c t i o n s of the v e r t i c a l s t r u t s and o r i f i c e r i n g and n e a r t h e s e w i n g r i n g c o u l d l e a d t o thrombus f o r m a t i o n and e x c e s s t i s s u e o v e r g r o w t h a t t h e s e locations. As s t a t e d p r e v i o u s l y , c l i n i c a l p a t h o l o g i c f i n d i n g s i n d i c a t e t h a t t h e s e r e g i o n s are the most prone to thrombus f o r m a t i o n and t i s s u e o v e r g r o w t h w i t h t h i s v a l v e . In a d d i t i o n , Roberts (1,62) s t a t e s that i n t i m a i p r o l i f e r a t i o n of the vessel wall adjacent to valve (mainly i n the a o r t i c p o s i t i o n ) is p r o b a b l y most s e v e r e w i t h the d i s c t y p e v a l v e s . The i n t i m a i p r o l i f e r a t i o n i s c a u s e d by l a r g e w a l l s h e a r s t r e s s e s .

(3) Ta]

Beall Valve

Disc Valve Description

The l o w - p r o f i l e B e a l l T e f l o n - d i s c m i t r a l v a l v e p r o s t h e s i s was i n t r o d u c e d f o r c l i n i c a l u s e i n 1967 (model 1 0 3 ) . The d i s c was made o f c o m p r e s s e d T e f l o n a n d t h e t i t a n i u m c a g e w a s c o v e r e d w i t h Teflon tubing. The v a l v e r i n g was t o t a l l y c o v e r e d w i t h D a c r o n v e l o u r i n an a t t e m p t t o a c h i e v e a low i n c i d e n c e o f thromboembolism. In 1968 because o f T e f l o n w e a r , t h e t h i c k n e s s and c o m p r e s s i o n o f t h e T e f l o n d i s c was i n c r e a s e d as was t h e thickness of the Teflon coating of the titanium cage. Later improvements o f t h e v a l v e d e s i g n (model 104) were d i r e c t e d toward i n c r e a s i n g i t s frustrum area without chaning i t s mounting d i a m e t e r , and on m a k i n g t h e m a t e r i a l s more d u r a b l e . The m o d e l 105 B e a l l v a l v e was i n t r o d u c e d i n 1 9 7 1 . In t h e model 105 t h e d i s c a n d s t r u t s w e r e c o v e r e d w i t h p y r o l i t i c c a r b o n . A f t e r problems o f s t r u t f r a c t u r e s were r e p o r t e d , the s t r u t s w e r e made s t r o n g e r a n d a new m e t h o d o f p a c k a g i n g w a s b e g u n . The model 106 v a l v e w i t h t h e t h i c k e r more d u r a b l e s t r u t s h a s been a v a i l a b l e s i n c e 1974 f o r a t r i o v e n t r i c u l a r v a l v e replacement, (b) Jji Vivo Results The c l i n i c a l p r e s s u r e d r o p r e s u l t s o b t a i n e d w i t h t h e B e a l l v a l v e i n d i c a t e t h a t i t i s e v e n more s t e n o t i c t h a n t h e K a y - S h i l e y d i s c valve. C a l c u l a t e d V A ' s v a r i e d between 1 . 4 and 2 . 3 c m 2 f o r valve s i z e s i n t h e 31 t o 41 mm r a n g e . One o f t h e m a j o r c l i n i c a l p r o b l e m s w i t h t h e B e a l l d i s c v a l v e was t h e e x c e s s i v e amount o f hemolysis i t caused ( 6 3 , 6 4 , 6 5 , 6 6 , 6 7 ) . I t has been s u g g e s t e d t h a t t h e D a c r o n v e l o u r c l o t h c o v e r i n g u s e d was t h e r e a s o n f o r the excessive hemolysis observed with t h i s valve (31). I t has



YOGANATHAN ET A L .


Figure

Figure

3.

2.

Kay-Shiley

Beall

dise

dise

valve,

valve

model

106



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a l s o been s u g g e s t e d t h a t d i s c wear o f t h e T e f l o n d i s c models exacerbated the native hemolysis of t h i s prosthesis (63). Nearly a l l p a t i e n t s who h a d t h i s v a l v e s u f f e r e d a t l e a s t m i l d i n t r a vascular hemolysis. A c o m p a r i s o n o f t h e TEC d a t a t e n d t o indicate that with anticoagulation therapy, thromboembolic c o m p l i c a t i o n s w i t h t h e B e a l l v a l v e were not as severe as those observed with the Kay-Shiley valve. But as s t a t e d by L e f r a k and S t a r r ( 4 1 2 ) , o n l y a few p u b l i c a t i o n s have a p p e a r e d i n w h i c h t i m e - r e l a t e d a n a l y s i s has been u t i l i z e d t o a n a l y z e t h e r a t e o f postoperative thromboemboli. Thrombus f o r m a t i o n c a u s i n g v a l v e d y s f u n c t i o n has a l s o been documented ( 5 3 , 6 3 , 6 7 - 7 0 ) . As s t a t e d by R o b e r t s e t a l . , ( 6 2 ) d i s c t y p e p r o s t h e s e s w i l l develop thrombotic material at the junctions of the v e r t i c a l struts and t h e o r i f i c e r i n g , a l o n g t h e v e r t i c a l s t r u t s and a c r o s s t h e face of the disc. U s u a l l y t h e amount o f t h r o m b u s on t h e s t r u t s or primary o r i f i c e i s not s u f f i c i e n t to i n t e r f e r e with the p r o p e r movement o f t h e d i s c , and c l i n i c a l e v i d e n c e o f s y s t e m i c e m b o l i c i n c i d e n t s a r e i n f r e q u e n t when t h e p r o s t h e t i c t h r o m b i are small. Large thrombi may, however, o b s t r u c t flow through t h e p r o s t h e s i s a n d may i m m o b i l i z e t h e d i s c . They a l s o s t a t e t h a t p r o s t h e s e s o f t h e d i s c t y p e may b e t i l t e d i n t h e c a g e b y t h r o b m u s o n o n e s i d e , o r t h r o m b u s may f i l l t h e e n t i r e s p a c e between t h e d i s c and t h e r i n g , c a u s i n g complete i m m o b i l i t y o f the poppet ( 6 2 ) . As o b s e r v e d w i t h t h e K a y - S h i l e y valve, t h r o m b u s f o r m a t i o n a n d e x c e s s t i s s u e o v e r g r o w t h may c a u s e i m p r o p e r m o t i o n o f t h e d i s c ( p r o p e r m o t i o n r e q u i r i n g movement up a n d d o w n t h e c a g e , a n d r o t a t i o n ) , t h e r e b y l e a d i n g t o g r o o v i n g and n o t c h i n g o f t h e d i s c (66,71,72). (c)

In V i t r o

Results

In v i t r o f l u i d dynamic s t u d i e s on t h e B e a l l d i s c v a l v e a r e v i r t u a l l y n o n e x i s t e n t i n t h e open l i t e r a t u r e . It i s doubtful i f a n y s u c h t e s t s were e v e n p e r f o r m e d by t h e v a l v e m a n u f a c t u r e r when t h e v a l v e s w e r e r e l e a s e d i n t h e m i d t o l a t e I 9 6 0 ' s . It i s , however, o u r o p i n i o n t h a t t h e v e l o c i t y and s h e a r f i e l d s downstream from t h i s valve a r e s i m i l a r t o those observed w i t h the K a y - S h i l e y and S t a r r - E d w a r d s d i s c v a l v e s . (d) Correlation The B e a l l d i s c v a l v e i s a v e r y s t e n o t i c valve design. If the assumptions about i t s i n v i t r o f l u i d dynamic c h a r a c t e r i s t i c s a r e c o r r e c t , t h e w a l l and t u r b u l e n t s h e a r s t r e s s c r e a t e d by t h i s v a l v e c o u l d e a s i l y damage t h e e n d o t h e l i a l l i n i n g o f t h e v e s s e l w a l l s , a n d c a u s e s u b l e t h a l a n d / o r l e t h a l damage t o b l o o d elements, respectively. In a d d i t i o n , i f t h e r e d c e l l s were to a t t a c h themselves t o the Dacron v e l o u r c l o t h c o v e r i n g , the s h e a r s t r e s s e s a d j a c e n t t o t h e v a l v e s u p e r s t r u c t u r e w o u l d be more t h a n s u f f i c i e n t t o c a u s e l e t h a l r e d c e l l damage (hemolysis). T h i s has been o b s e r v e d c l i n i c a l l y w i t h t h i s p r o s t h e s i s and t h e c l o t h covered S t a r r - E d w a r d s ball valves. The r e g i o n o f f l o w s t a s i s a d j a c e n t t o t h e d o w n s t r e a m f a c e o f t h e



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d i s c and t h e r e g i o n s o f f l o w s e p a r a t i o n a t t h e j u n c t i o n s o f t h e v e r t i c a l s t r u t s and t h e o r i f i c e r i n g c o u l d l e a d t o a b u i l d u p o f t h r o m b o t i c m a t e r i a l and e x c e s s t i s s u e o v e r g r o w t h a t t h o s e l o c a t i o n s a s h a s b e e n o b s e r v e d o n some r e c o v e r e d B e a l l v a l v e s . The e a r l y model B e a l l v a l v e was b r i e f l y u t i l i z e d i n t h e a o r t i c p o s i t i o n b u t i t s use i n t h i s l o c a t i o n was a b a n d o n e d b e c a u s e o f o b s t r u c t i v e , t h r o m b o g e n i c and wear c h a r a c t e r i s t i c s ( 1 , 6 2 ) . Furthermore, Roberts i n his pathologic studies observed that d i s c valves i n the a o r t i c p o s i t i o n cause i n t i m a i p r o l i f e r a t i o n o f t h e a o r t i c r o o t , as a r e s u l t o f e x c e s s i v e w a l l s h e a r s t r e s s e s (1,62),

(4) B j o r k - S h i l e y T i l t i n g Disc Valve Taj valve Description The B j o r k - S h i l e y t i l t i n g d i s c p r o s t h e s i s has been i n c l i n i c a l use s i n c e J a n u a r y 1969. The p r o s t h e s i s has u n d e r g o n e various m o d i f i c a t i o n s i n d e s i g n and m a t e r i a l s s i n c e i t s i n i t i a l u s e . The o r i g i n a l B j o r k - S h i l e y v a l v e had a D e l r i n d i s c . Although Delrin had e x c e l l e n t w e a r c h a r a c t e r i s e s i t had a p r o p e n s i t y t o a b s o r b m o i s t u r e d u r i n g steam a u t o c l a v i n g , a p r o c e d u r e n o t recommended by t h e m a n u f a c t u r e r . Thus, the d i s c i f improperly s t e r i l i z e d by t h i s method c o u l d e n l a r g e and p r o d u c e t e m p o r a r y irregular valve function. S i n c e t h e s p r i n g o f 1971 t h e d i s c h a s b e e n made o f p y r o l y t i c c a r b o n w h i c h i s e x t r e m e l y d u r a b l e and does not absorb moisture d u r i n g steam a u t o c l a v i n g . In t h i s v a l v e d e s i g n a f r e e - f l o a t i n g d i s c i s s u s p e n d e d between two e c c e n t r i c a l l y situated Stellite struts. The v a l v e p r e s e n t l y t i l t s open t o an a n g l e o f 6 0 ° i n b o t h a o r t i c and m i t r a l models a l t h o u g h i n t h e e a r l i e r D e l r i n d i s c m o d e l t h e m i t r a l p r o s t h e s i s was d e s i g n e d t o t i l t o p e n t o an a n g l e o f o n l y 5 0 ° . The d i s c s i t s i n s i d e t h e base r i n g i n the c l o s e d p o s i t i o n thus p r e v e n t i n g over l a p p i n g and r e d u c i n g m e c h a n i c a l h e m o l y s i s . The S t e l l i t e b a s e r i n g i s p a r t i a l l y c o v e r e d by a t h i n T e f l o n s u t u r e r i n g . This valve d e s i g n has t h e a d v a n t a g e o f a l a r g e r a t i o o f o r i f i c e d i a m e t e r t o annulus diameter. When t h e B j o r k - S h i l e y v a l v e i s s u t u r e d i n p l a c e t h e c a g e c a n be r o t a t e d w i t h i n t h e s e w i n g r i n g b y m e a n s o f a v a l v e h o l d e r i n o r d e r t o e n s u r e f r e e movement o f t h e d i s c . In J u n e 1976 P r o f e s s o r V i k i n g 0 . B j o r k i m p l a n t e d t h e f i r s t modified B j o r k - S h i l e y valve with a convexo-concave ( C . C . ) d i s c . The m o d i f i e d v a l v e was d e s i g n e d a c c o r d i n g t o D r . B j o r k t o improve the conventional B j o r k - S h i l e y valve i n three r e s p e c t s : (1) p r o v i d e i n c r e a s e d s t r e n g t h o f t h e v a l v e by m a k i n g t h e i n l e t s t r u t an i n t e g r a l p a r t o f t h e o r i f i c e r i n g and d o u b l i n g i t s c r o s s - s e c t i o n a l a r e a (2) i m p r o v e t h e h y d r o d y n a m i c s (3) reduction i n t h e a r e a o f low f l o w and s t a g n a t i o n b e h i n d t h e d i s c . The d e s i g n change i n c l u d e s the convexo-concave c o n f i g u r a t i o n of the d i s c and a p i v o t p o i n t w h i c h has been moved s e v e r a l m i l l i m e t e r s d o w n s t r e a m so t h a t t h e d i s c i n t h e o p e n p o s i t i o n i s moved f u r t h e r out of the o r i f i c e r i n g . Valves manufactured a f t e r September 1975 have a r a d i o - o p a q u e t a n t a l u m l o o p i n c o r p o r a t e d i n t h e p y r o l y t i c carbon d i s c to allow evaluation of the opening angle of the d i s c .


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C l i n i c a l hemodynamic r e s u l t s i n d i c a t e t h a t t h e Bjork-Shiley v a l v e has i m p r o v e d p r e s s u r e d r o p c h a r a c t e r i s i t c s compared t o t h e c e n t r a l l y o c c l u d i n g ( b a l l and d i s c ) and p o r c i n e v a l v e prostheses. C a l c u l a t e d valve areas (VA's) varied from 1.06 to 2 . 5 6 c m 2 f o r a o r t i c v a l v e s i z e s o f 1 9 t o 31 mm, a n d 1 . 8 to 2 . 6 c m 2 f o r m i t r a l v a l v e s i z e s o f 2 7 a n d 2 9 mm. The l i m i t e d h e m o d y n a m i c d a t a t e n d t o i n d i c a t e no s i g n i f i c a n t d i f f e r e n c e s i n t h e p r e s s u r e d r o p c h a r a c t e r i s t i c s o f t h e s p h e r i c a l and convexo-concave d i s c a o r t i c valves. Due t o i t s w o r l d w i d e p o p u l a r i t y t h e r e i s a l a r g e amount o f l i t e r a t u r e i n t h e m e d i c a l f i e l d on t h i s p r o s t h e s i s . Hemolysis data i n d i c a t e that the B j o r k - S h i l e y p r o s t h e s i s can cause m i l d to moderate h e m o l y s i s . P a t i e n t s w i t h t h i s p r o s t h e s i s , however, r a r e l y develop anemia because t h e body u s u a l l y compensates adequately f o r the h e m o l y s i s c a u s e d by t h e v a l v e . The p r o s t h e s i s has a TEC rate o f a b o u t 4 t o 6% p e r p t . y r . The m a j o r p r o b l e m w i t h t h e B j o r k - S h i l e y valve i s i t s p o t e n t i a l to thrombose, sometimes c a t a s t r o p h i c a l l y , e s p e c i a l l y i n p a t i e n t s not on a n t i c o a g u l a t i o n therapy (53,55,73-83). In a d d i t i o n t o thrombus f o r m a t i o n , e x c e s s t i s s u e overgrowth has a l s o been o b s e r v e d on r e c o v e r e d B j o r k - S h i l e y v a l v e s . Please note t h a t the above r e f e r e n c e s a l l p e r t a i n t o the s t a n d a r d (i.e.: s p h e r i c a l d i s c ) B j o r k - S h i l e y model ( e x c e p t r e f . 73,83). T h e r e h a v e b e e n no l o n g t e r m s t u d i e s o n t h e c o n v e x o - c o n c a v e m o d e l , and thrombus f o r m a t i o n on t h i s model has so f a r o n l y been r e p o r t e d i n two a r t i c l e s ( 7 3 , 8 3 ) . Thrombus f o r m a t i o n m a i n l y o c c u r s on t h e o u t f l o w f a c e o f t h e d i s c e s p e c i a l l y i n the w e l l , and a l o n g t h e s t r u t s i n the m i n o r o u t f l o w r e g i o n . However, thrombus f o r m a t i o n on b o t h t h e i n f l o w and o u t f l o w f a c e s o f t h e d i s c h a s b e e n o b s e r v e d i n some r e c o v e r e d v a l v e s . Excess t i s s u e overgrowth i s observed mainly along the sewing r i n g of the minor outflow r e g i o n . The amounts o f t h r o m b u s f o r m a t i o n and/or t i s s u e o v e r g r o w t h o b s e r v e d on r e c o v e r e d B j o r k - S h i l e y a o r t i c and m i t r a l v a l v e s has v a r i e d f r o m t o t a l v a l v e o c c l u s i o n t o a thin layer. I n some i n s t a n c e s t h e c o m b i n a t i o n o f thrombus f o r m a t i o n and t i s s u e o v e r g r o w t h has grown i n s u c h a manner t o impede t h e c o m p l e t e o p e n i n g o f t h e t i l t i n g d i s c . In o t h e r i n s t a n c e s , t h e d i s c h a s b e e n f o u n d t o be h e l d i m m o b i l i z e d i n an o p e n p o s i t i o n by t h e v e g e t a t i o n . Therefore, i t i s of u t m o s t i m p o r t a n c e t h a t t h e p h y s i c i a n be a b l e t o m o n i t o r t h e motion of the d i s c using c i n e f l u o r o s c o p y . (c) In V i t r o Results The i n v i t r o p r e s s u r e d r o p r s u l t s i n d i c a t e t h a t t h e Bjork-Shiley v a l v e s have c a l c u l a t e d VA's o f 1.37 t o 3 . 4 0 c m 2 f o r a o r t i c and m i t r a l v a l v e s i n t h e 21 t o 31 mm s i z e r a n g e . There does not s e e m t o be a n y s i g n i f i c a n t d i f f e r e n c e i n t h e p r e s s u r e d r o p a n d r e g u r g i t a t i o n c h a r a c t e r i s t i c s between the s p h e r i c a l and convexoconcave d i s c v a l v e s . Regurgitation data tend to i n d i c a t e that



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a t low h e a r t r a t e s and low c a r d i a c o u t p u t s t h e B j o r k - S h i l e y v a l v e does have a s i g n i f i c a n t r e g u r g i t a n t volume ( 1 6 ) . For e x a m p l e , t h e r e c e n t s t u d y by D e l l s p e r g e r e t a l . showed t h a t t h e 2 7 mm B j o r k - S h i l e y ( c - c ) a o r t i c v a l v e h a d a r e g u r g i t a n t volume as h i g h a s 1 3 . 0 c n r / b e a t a t a h e a r t r a t e o f 50 b e a t s / m i n (16). T h e r e have b e e n many f l o w v i s u a l i z a t i o n s t u d i e s c o n d u c t e d on t h e B j o r k - S h i l e y v a l v e i n b o t h t h e a o r t i c and m i t r a l p o s i t i o n s (41,42,48,84-87). W r i g h t h a s s t u d i e d t h e v a l v e ( s i z e 2 5 mm) under p u l s a t i l e flow i n a curved a o r t a ( 4 1 , 8 7 ) . When t h e v a l v e was o r i e n t e d so t h a t t h e d i s c o p e n e d t o w a r d s t h e o u t e r c u r v e o f t h e a o r t a , a c l o c k w i s e r o t a t i n g v o r t e x was f o r m e d i n t h e a s c e n d i n g a o r t a d u r i n g most o f s y s t o l e . O r i e n t a t i o n of the d i s c towards the i n s i d e curve produced a r e l a t i v e l y narrow, tangential jet. When t h e v a l v e w a s m o u n t e d t o o p e n t o w a r d s t h e n o n - c o r o n a r y s i n u s , a d o u b l e h e l i x s w i r l i n g f l o w s t r e a m was produced. I n t h e m i t r a l p o s i t i o n ( s i z e 2 9 mm v a l v e ) he o b s e r v e d t h a t a l a r g e two d i m e n s i o n a l v o r t e x formed w h i c h d o m i n a t e d t h e l e f t v e n t r i c l e f o r most o f d i a s t o l e . D e l l s p e r g e r and W i e t i n g s t u d i e d a 2 9 mm v a l v e i n t h e m i t r a l p o s i t i o n ( 4 8 ) . They observed a region of s t a s i s underneath the outflow face of the d i s c during a major portion of d i a s t o l e . A s i m i l a r region of s t a g n a t i o n c a n b e o b s e r v e d i n t h e r e s u l t s o b t a i n e d b y 01 i n i n an a o r t i c f l o w chamber ( 4 2 ) . Flow v i s u a l i z a t i o n s t u d i e s under p u l s a t i l e f l o w c o n d i t i o n s i n o u r l a b o r a t o r y have shown t h a t there i s a large region of s t a s i s underneath the outflow faces o f t h e a o r t i c and m i t r a l d i s c s d u r i n g t h e m a j o r p o r t i o n s o f s y s t o l e and d i a s t o l e , r e s p e c t i v e l y ( 8 8 ) . The s t u d i e s have a l s o shown q u a l i t a t i v e l y t h a t r e g i o n s o f s t a g n a t i o n o b s e r v e d with the convexo-concave valves are smaller than those observed with the s p e r i c a l d i s c valves. Schramm e t a l . , s t u d i e d a 2 5 mm s p h e r i c a l d i s c v a l v e i n a n a o r t i c c h a m b e r a t a s t e a d y f l o w r a t e o f 18 1 / m i n ( 8 5 ) . They have o b s e r v e d j e t type f l o w immediately downstream from the major o r i f i c e , which i s d i r e c t e d t a n g e n t i a l l y towards the w a l l . They have a l s o o b s e r v e d a large region of stagnation across the outflow face of the disc. M e a s u r e m e n t s o n a 2 5 mm c o n v e x o - c o n c a v e v a l v e u n d e r t h e same c o n d i t i o n s s h o w e d : ( i ) a more p r o n o u n c e d j e t t h r o u g h t h e m a j o r o r i f i c e and ( i i ) a s m a l l e r r e g i o n o f s t a g n a t i o n a c r o s s the o u t f l o w face of the d i s c . F i g l i o l a h a s made s t e a d y f l o w v e l o c i t y a n d s h e a r s t r e s s m e a s u r e m e n t s d o w n s t r e a m f r o m a 2 5 mm s p h e r i c a l d i s c a o r t i c v a l v e (47,89). A t a f l o w r a t e o f 2 5 1 / m i n he m e a s u r e d a m a x i m u m w a l l s h e a r s t r e s s o f 722 d y n e s / c m 2 and an o c c l u d e r w a l l s h e a r 2 s t r e s s ( r e s o l v e d on t h e u p p e r s i d e o f o c c l u d e r ) o f 440 d y n e s / c m . He a l s o m o n i t o r e d a m a x i m u m t u r b u l e n t s h e a r s t r e s s o f 5 4 5 d y n e s / c m 2 , a 2 5 mm d o w n s t r e a m f r o m t h e v a l v e . His v e l o c i t y measurements a l s o showed a l a r g e r e g i o n o f s t a g n a t i o n a c r o s s t h e o u t f l o w face of the d i s c . T i l l m a n has m e a s u r e d t h e " w a l l " (i.e.: s u r f a c e ) s h e a r s t r e s s e s a l o n g the o r i f i c e r i n g i n t h e m a j o r and m i n o r o u t f l o w r e g i o n s o f an a o r t i c v a l v e under p u l s a t i l e f l o w



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(49,90). D u r i n g s y s t o l e he m e a s u r e d m a x i m u m s u r f a c e s h e a r s t r e s s e s o f 150 d y n e s / c m 2 a n d 50 d y n e s / c m 2 i n t h e m a j o r a n d minor o r i f i c e s , r e s p e c t i v e l y . D u r i n g d i a s t o l e he m e a s u r e d a maximum s h e a r s t r e s s o f a b o u t 250 d y n e s / c m 2 i n t h e m i n o r orifice. P h i l l i p s a n d h i s c o - w o r k e r s ( 8 6 , 9 1 ) made v e l o c i t y measurements under p u l s a t i l e f l o w c o n d i t i o n s downstream from a 2 5 mm c o n v e x o - c o n c a v e a o r t i c v a l v e . At peak s y s t o l e (peak f l o w o f 45 1/min) t h e y o b s e r v e d j e t t i n g t h r o u g h t h e m a j o r o r i f i c e w i t h v e l o c i t i e s o n t h e o r d e r o f 3 5 0 c m / s , 14 mm d o w n s t r e a m f r o m the valve. RMS m e a s u r e m e n t s o f t h e a x i a l v e l o c i t y s h o w e d l a r g e t u r b u l e n c e f l u c t u a t i o n s ( o n t h e o r d e r o f 140 c m / s ) . They e s t i m a t e d t h e maximum t u r b u l e n t s h e a r s t r e s s d u r i n g s y s t o l e t o be o n t h e o r d e r o f 2 0 0 0 t o 6 5 0 0 d y n e s / c m 2 . Yoganathan e t a l . , have measured v e l o c i t i e s and s h e a r s t r e s s e s d o w n s t r e a m f r o m a 2 7 mm s p h e r i c a l d i s c v a l v e a s w e l l as a c o n v e x o - c o n c a v e v a l v e i n t h e a o r t i c p o s i t i o n . Experiments w e r e c o n d u c t e d a t a s t e a d y f l o w r a t e o f 25 1 / m i n , (60,81,92). The measurements w i t h t h e s p h e r i c a l d i s c v a l v e i d e n t i f i e d a z o n e o f s t a g n a t i o n a b o u t 2 0 mm w i d e n e a r t h e a o r t i c f a c e o f the d i s c . The a v e r a g e v e l o c i t i e s i n t h e m a j o r and m i n o r o u t f l o w r e g i o n s w e r e a r o u n d 100 a n d 25 c m / s , r e s p e c t i v e l y , a n d t h e c o r r e s p o n d i n g peak shear s t r e s s e s a d j a c e n t to the sewing r i n g w e r e a p p r o x i m a t e l y 700 and 150 d y n e s / c m 2 . A maximum w a l l s h e a r s t r e s s o f 1390 d y n e s / c m 2 was m e a s u r e d . With the convexo-concave v a l v e t h e r e g i o n o f s t a g n a t i o n w a s o b s e r v e d t o b e 10 mm w i d e , a n d t h e a v e r a g e v e l o c i t i e s i n t h e m a j o r and m i n o r o u t f l o w r e g i o n s w e r e a r o u n d 90 a n d 40 c m / s e c , r e s p e c t i v e l y . Peak s h e a r s t r e s s e s on s u r f a c e s a d j a c e n t t o t h e s e w i n g r i n g i n t h e m a j o r and m i n o r o u t f l o w r e g i o n s were about 5 0 0 - 6 0 0 and 3 0 0 - 3 5 0 d y n e s / c m 2 , respectively. The c o n v e x o - c o n c a v e v a l v e d o e s , h o w e v e r , d i r e c t r e l a t i v e l y high flow from the major outflow r e g i o n towards one o f t h e s i n u s e s o f V a l s a l v a d e p e n d i n g on i t s o r i e n t a t i o n . W a l l s h e a r s t r e s s e s o n t h e o r d e r o f 1750 d y n e s / c m 2 w e r e o b s e r v e d o n t h e s i n u s w a l l t o w a r d s w h i c h t h e h i g h f l o w was directed. T u r b u l e n t measurements w i t h both models i n d i c a t e d t u r b u l e n t s h e a r s t r e s s e s on t h e o r d e r o f 500 t o 2000 d y n e s / c m i m m e d i a t e l y d o w n s t r e a m ( 3 t o 1 5 mm) f r o m t h e v a l v e , (d) Correlation The i n v i v o and i n v i t r o p r e s s u r e m e a s u r e m e n t s i n d i c a t e t h a t i n t h e l a r g e r s i z e s and under r e s t i n g c o n d i t i o n s t h e p r e s s u r e drop c h a r a c t e r i s t i c s of the B j o r k - S h i l e y valve are q u i t e satisfactory. However, under e x e r c i s e c o n d i t i o n s and/or i n t h e s m a l l e r s i z e s t h e v a l v e c o u l d become m i l d t o m o d e r a t e l y stenotic. This i s e s p e c i a l l y true i n the m i t r a l p o s i t i o n . The i n v i t r o s t u d y by D e l l s p e r g e r e t a l . , (16) s u g g e s t t h a t a t low h e a r t r a t e s and low c a r d i a c o u t p u t s t h e i n v i v o r e g u r g i t a t i o n v o l u m e s w i t h t h i s p r o s t h e s i s c o u l d become significant. The w a l l s h e a r s t r e s s e s c r e a t e d by t h i s v a l v e


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c o u l d c a u s e s u b l e t h a l a n d / o r l e t h a l damage t o t h e e n d o t h e l i a l l i n i n g of vessel w a l l s e s p e c i a l l y i n the a o r t i c p o s i t i o n . T u r b u l e n t shear s t r e s s e s are l a r g e enough to cause s u b l e t h a l a n d / o r l e t h a l damage t o r e d c e l l s and p l a t e l e t s t h e r e b y r e d u c i n g their half-lifes. Therefore, i t i s not s u r p r i s i n g to observe c l i n i c a l l y , h e m o l y s i s and t h r o m b o e m b o l i c p r o b l e m s w i t h t h i s prosthesis. The i n v i t r o s t u d i e s have documented c o n c l u s i v e l y t h a t t h e B j o r k - S h i l e y v a l v e c r e a t e s two unequal r e g i o n s o f f l o w . There i s a region of s t a s i s underneath the outflow face of the d i s c and low f l o w t h r o u g h t h e m i n o r o u t f l o w r e g i o n . It i s therefore f a i r l y o b v i o u s t h a t thrombus f o r m a t i o n w i l l o c c u r on t h e o u t f l o w f a c e o f t h e d i s c and a l o n g t h e s t r u t s i n t h e m i n o r outflow region. As o b s e r v e d by Y o g a n a t h a n e t a l . , o n c e t h e thrombus f o r m a t i o n and t i s s u e o v e r g r o w t h b e g i n s on t h e downstream s i d e o f t h e v a l v e t h e f l o w f i e l d becomes e v e n more favorable f o r f u r t h e r t h r o m b u s f o r m a t i o n and t i s s u e o v e r g r o w t h on t h e valve superstructure (81). The r e c o v e r e d B j o r k - S h i l e y v a l v e s w h i c h have thrombus on b o t h t h e o u t f l o w and i n f l o w f a c e s o f t h e d i s c , p r o b a b l y had thrombus o c c u r on t h e o u t f l o w f a c e o f t h e disc first. The i n i t i a l t h r o m b u s f o r m a t i o n p r o b a b l y c a u s e s unfavorable flow c o n d i t i o n s immediately adjacent to the i n f l o w f a c e , t h e r e b y c a u s i n g thrombus f o r m a t i o n at t h a t l o c a t i o n as w e l l . The l o w f l o w and low s h e a r i n t h e m i n o r o u t f l o w r e g i o n would encourage the growth o f excess f i b r o u s t i s s u e along the sewing r i n g i n that r e g i o n . As has been o b s e r v e d i n t h e r e c o v e r e d v a l v e s , t h e c o m b i n a t i o n o f thrombus f o r m a t i o n and t i s s u e overgrowth can produce c a t a s t r o p h i c r e s u l t s . The s m a l l e r r e g i o n o f s t a g n a t i o n , and t h e b e t t e r d i s t r i b u t i o n o f f l o w between t h e m a j o r and m i n o r o r i f i c e s o b s e r v e d w i t h t h e c o n v e x o - c o n c a v e v a l v e , may h o p e f u l l y r e d u c e t h e p r o b l e m s o f thrombus f o r m a t i o n on t h e o u t f l o w f a c e o f t h e d i s c , and e x c e s s t i s s u e growth along the sewing r i n g of the minor o r i f i c e r e g i o n . (5) Hancock P o r c i n e Valve Ta") Valve D e s c r i p t i o n The H a n c o c k p r o c i n e b i o p r o s t h e s i s , p r e p a r e d by t h e S t a b i l i z e d G l u t a r a l d e h y d e P r o c e s s ( " S G P " ) has been i n c l i n i c a l use s i n c e 1970. P o r c i n e v a l v e s p r e s e r v e d by t h e "SGP" p r o c e s s a r e s u t u r e d to a Dacron c l o t h - c o v e r e d f l e x i b l e polypropylene s t e n t . It s h o u l d be n o t e d t h a t t h e p o r c i n e v a l v e l e a f l e t s a r e c o m p o s e d o f natural polymeric materials. A radio-opaque S t e l l i t e metal r i n g e n c i r c l e s t h e s t e n t and h e l p s m a i n t a i n o r i f i c e shape and proper l e a f l e t coaptation. Model 242 i s used f o r a o r t i c v a l v e r e p l a c e m e n t w h i l e model 342 i s used i n t h e m i t r a l and t r i c u s p i d valve areas. These models d i f f e r o n l y i n the shape o f t h e i r sewing r i n g s . The Hancock M o d i f i e d O r i f i c e a o r t i c b i o p r o s t h e s i s (HMO-250) d i f f e r s f r o m t h e o t h e r two m o d e l s by h a v i n g r e p l a c e d the r i g h t coronary l e a f l e t , and c o n t a i n s a p o r t i o n o f s e p t a l e n d o c a r d i u m w i t h a n o n - c o r o n a r y l e a f l e t o f an a p p r o p r i a t e s i z e . T h i s v a l v e m o d i f i c a t i o n was a c c o m p l i s h e d i n an a t t e m p t t o



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i n c r e a s e the e f f e c t i v e flow o r i f i c e f o r use i n p a t i e n t s w i t h a small a o r t i c annulus. The f i r s t c l i n i c a l i m p l a n t o f a HMO-250 b i o p r o s t h e s i s was i n O c t o b e r 1 9 7 6 . (b) In V i v o R e s u l t s S i n c e t h e Hancock v a l v e i s t h e g r a n d f a t h e r o f t h e t i s s u e v a l v e b i o p r o s t h e s e s , t h e r e a r e many a r t i c l e s i n t h e o p e n l i t e r a t u r e on i t s l o n g - t e r m c l i n i c a l p e r f o r m a n c e . This valve i s u t i l i z e d i n two d e s i g n s , t h e s t a n d a r d model and t h e m o d i f i e d . The s t a n d a r d model a o r t i c v a l v e has c a l c u l a t e d V A ' s o f 0 . 9 7 t o 1 . 8 c m 2 f o r v a l v e s i z e s o f 1 9 t o 2 7 mm. In the m i t r a l p o s i t i o n c a l c u l a t e d V A ' s ranged from 1 . 3 t o 2 . 9 c m 2 f o r valves size o f 2 3 t o 3 5 mm. T h e m o d i f i e d o r i f i c e a o r t i c v a l v e h a d V A ' s o f 0 . 8 9 t o 1 . 7 5 c m 2 f o r v a l v e s i z e s o f 1 9 t o 2 5 mm. From a comparison o f the i n vivo pressure drop r e s u l t s , i t i s not immediately obvious that the modified o r i f i c e valves are less s t e n o t i c t h a n t h e s t a n d a r d model v a l v e s . As s t a t e d by R o s s i t e r e t a l . , (93) t h e hemodynamic d i f f e r e n c e s between t h e two v a l v e types a r e s m a l l , and t h e p u t a t i v e c l i n i c a l advantages i n h e r e n t i n t h e u s e o f t h e m o d i f i e d o r i f i c e v a l v e r e m a i n t o be c o m p l e t e l y defined. Both d e s i g n s o f Hancock v a l v e s a r e , however, more s t e n o t i c compared t o t h e I o n e s c u - S h i l e y p e r i c a r d i a l v a l v e . C l i n i c a l l y s i g n i f i c a n t hemolysis i s not a major problem w i t h this valve. M i l d amounts o f h e m o l y s i s h a v e , h o w e v e r , been documented ( 9 4 , 9 5 ) . Thromboembolic c o m p l i c a t i o n s and thrombus f o r m a t i o n o n t h e v a l v e l e a f l e t s have a l s o been w e l l documented (93,96-100). The l i t e r a t u r e i n d i c a t e s t h a t p a t i e n t s w i t h H a n c o c k v a l v e s h a v e T E C r a t e s o f a b o u t 2 t o 5% p e r p t . y r . , the higher rates o c c u r r i n g i n m i t r a l valve patients with a t r i a l fibrillation. Thrombus f o r m a t i o n on t h e v a l v e s t r u c t u r e ( i . e . , sewing r i n g and l e a f l e t s ) and t h r o m b o s i s o f t h e Hancock v a l v e , i n both t h e a o r t i c and m i t r a l p o s i t i o n a r e w e l l documented i n t h e literature (96,99-107). In a m a j o r i t y o f t h e documented cases o f v a l v e t h r o m b o s i s , t h e t h r o m b o t i c m a t e r i a l was found a t t a c h e d t o t h e d o w n s t r e a m s e w i n g r i n g a n d up a l o n g t h e o u t f l o w s u r f a c e o f o n e o r more o f t h e l e a f l e t s . T h r o m b o t i c m a t e r i a l s have a l s o on o c c a s i o n s been o b s e r v e d on t h e i n f l o w o r i f i c e and i n f l o w surfaces of the l e a f l e t s , mainly i n the mitral position. On many o c c a s i o n s t h e t h r o m b o t i c m a t e r i a l i n i t i a l l y s t a r t e d o n the outlfow face o f the m u s c l e - s h e l f l e a f l e t s (102,105,108,109). Thrombus f o r m a t i o n on o n e o r more l e a f l e t s has a t t i m e s l e d to t h r o m b o t i c o c c l u s i o n o f t h e p r o s t h e s i s and demise o f t h e patient (102,104-107,109,110). Detailed pathologic studies on r e c o v e r e d Hancock p o r c i n e v a l v e s by F e r r a n s e t a l . , ( 1 0 1 , 1 0 3 , 1 1 1 ) , a n d S p r a y a n d R o b e r t s ( 1 0 6 ) h a v e r e v e a l e d some very i n t e r e s t i n g information. Thrombi a r e commonly o b s e r v e d on t h e o u t f l o w s u r f a c e s (more s o t h a n o n t h e i n f l o w s u r f a c e s ) o f Hancock p o r c i n e v a l v e s , i n s p i t e o f t h e low i n c i d e n c e o f c l i n i c a l l y apparent thromboembolic episodes. Subsequent s t u d i e s



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by o t h e r s have c o n f i r m e d t h e s e f i n d i n g s ( 1 0 1 , 1 0 4 ) . Ferrans et a l . , (101) state that their ultra-structural observations p o i n t t o t h e p o s s i b i l i t y t h a t s m a l l f i b r i n d e p o s i t s and p l a t e l e t a g g r e g a t e s f o r m c o n t i n u o u s l y on t h e s u r f a c e s o f t h e l e a f l e t s and b e c a u s e o f t h e m e c h a n i c a l f o r c e s t o w h i c h t h e y a r e s u b j e c t e d , the m a j o r i t y of such d e p o s i t s o r aggregates are shed from the s u r f a c e s i n t o t h e b l o o d s t r e a m b e f o r e t h e y have had an o p p o r t u n i t y t o grow t o a l a r g e r s i z e . They a l s o s t a t e the f a c t that f i b r i n t h r o m b i d e p o s i t s and c e l l s were numerous on t h e outflow surfaces. T h i s f i n d i n g i s i n agreement w i t h the concept t h a t t h e f o r c e s o f f l o w ( s h e a r s t r e s s ) a r e g r e a t e r on t h e i n f l o w t h a n on the o u t f l o w s u r f a c e s o f p o r c i n e v a l v e s . Therefore fibrin a n d t h r o m b o t i c d e p o s i t s o n t h e o u t f l o w s u r f a c e s w o u l d be l e s s e a s i l y r e m o v e d a n d w o u l d be e x p e c t e d t o g r o w l a r g e r a n d s h o w e v i d e n c e o f o r g a n i z a t i o n as o b s e r v e d i n t h e i r s t u d y (101) and t h e s t u d y o f S p r a y and R o b e r t s (106). One o f t h e m a j o r c l i n i c a l p r o b l e m s o f H a n c o c k p o r c i n e v a l v e s i s the c a l c i f i c a t i o n of the valve l e a f l e t s . The d e v e l o p m e n t of c a l c i f i c a t i o n a p p e a r s t o be a c c e l e r a t e d i n c h i l d r e n a n d y o u n g adults (96,98,100,103,104,112-115). Ferrans et a l . , ( 1 0 3 ) in an e x c e l l e n t p a t h o l o g i c s t u d y o b s e r v e d t h a t t h e two m a i n s i t e s of d e p o s i t i o n of c a l c i u m phosphate i n porcine valves are i n the c o n n e c t i v e t i s s u e o f t h e c u s p s and i n t h e s m a l l t h r o m b i on t h e leaflet surfaces. C a l c i f i c d e p o s i t s on the v a l v e l e a f l e t s g e n e r a l l y lead to p r o s t h e t i c valve s t e n o s i s , because c a l c i f i c a t i o n causes impaired l e a f l e t m o b i l i t y . However, i t can a l s o l e a d to valve r e g u r g i t a t i o n . Examinations o f r e c o v e r e d Hancock v a l v e s i n d i c a t e t h a t c a l c i f i c a t i o n i s a s s o c i a t e d w i t h one ( g e n e r a l l y t h e m u s c l e - s h e l f l e a f l e t ) o r more o f t h e l e a f l e t s . It i s a l s o not unusual to f i n d that c a l c i f i c a t i o n of the l e a f l e t s t o be a s s o c i a t e d w i t h t h r o m b o t i c d e p o s i t s i n and a r o u n d t h e same l o c a t i o n s . F e r r a n s e t a l . , (103) o b s e r v e d t h a t calcific d e p o s i t s a s s o c i a t e d w i t h v e g e t a t i o n and t h r o m b i , contained remnants o f p l a t e l e t s and l e u k o c y t e s t h a t a p p e a r e d t o have been t r a p p e d w i t h i n a mesh o f f i b r i n s t a n d a r d s . Varying degrees o f f i b r o u s t i s s u e o v e r g r o w t h on r e c o v e r e d Hancock p o r c i n e v a l v e s have a l s o been o b s e r v e d d u r i n g g r o s s p a t h o l o g i c e x a m i n a t i o n s (97,100,102,104,113,116-119). Although the greatest amount o f f i b r o u s t i s s u e o v e r g r o w t h has been o b s e r v e d a r o u n d t h e downstream s e w i n g r i n g and t h e o u t f l o w b a s e s o f t h e v a l v e c u p s , t i s s u e o v e r g r o w t h on t h e i n l e t a s p e c t o f t h e s e w i n g r i n g and v a l v e c u s p s has a l s o been o b s e r v e d . The f i b r o u s t i s s u e g r o w t h may b e r e l a t e d t o t h e c a l c i f i c a t i o n p r o c e s s ( 1 0 3 ) . (c) In v i t r o R e s u l t s The s t a n d a r d Hancock v a l v e (model 242 and 342) has V A ' s i n t h e range o f 1.12 t o 1 . 9 3 cm2 f o r b o t h a o r t i c and m i t r a l v a l v e s i n t h e 1 9 a n d 3 3 mm s i z e r a n g e . The V A ' s f o r t h e m o d i f i e d o r i f i c e v a l v e s ( m o d e l 2 5 0 ) v a r i e d f r o m 1 . 0 2 t o 2 . 0 1 c n r f o r t h e 19 t o 2 5 mm v a l v e s i z e s . Gabbay e t a l . , (120) s t a t e t h a t t h e r e i s no



8.

YOGANATHAN ET A L .


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d i f f e r e n c e i n p r e s s u r e drop c h a r a c t e r i s t i c s between the Carpentier-Edwards and m o d i f i e d o r i f i c e Hancock v a l v e s o f corresponding sizes. Recent s t u d i e s i n our l a b o r a t o r y have confirmed these f i n d i n g s . R e g u r g i t a t i o n was a l m o s t nonexistent («* 1 c n r / b e a t ) f o r t h e Hancock v a l v e s . Flow v i s u a l i z a t i o n s t u d i e s ( 4 1 , 8 5 , 8 7 , 8 8 ) i n d i c a t e t h a t t h e f l o w t h a t emerges from t h e Hancock v a l v e s , s t a n d a r d and modified o r i f i c e , i s j e t - l i k e . Schramm e t a l . , (85) i n t h e i r s t u d y s h o w e d t h a t t h e r e was no r e a t t a c h m e n t o f t h e j e t . At a s t e a d y f l o w r a t e o f 181/min they observed a peak j e t velocity o f 180 cm/s w i t h a s i z e 25 m o d i f i e d o r i f i c e v a l v e . Wright (41,87) i n his studies observed a vortex swirl i n addition to the j e t . Y o g a n a t h a n e t a l . , i n t h e i r s t u d y w i t h a s i z e 2 7 mm s t a n d a r d v a l v e a n d a s i z e 2 5 mm m o d i f i e d o r i f i c e v a l v e , observed t h a t t h e j e t was n o t s y m m e t r i c and was s k e w e d t o w a r d s o n e s i d e (88). Flow s e p a r a t i o n o c c u r r e d at t h e downstream edge o f the leaflets. The a n n u l a r r e g i o n b e t w e e n t h e o u t f l o w s u r f a c e o f t h e l e a f l e t s and t h e f l o w c h a n n e l w a l l was r e l a t i v e l y s t a g n a n t . High s p e e d p h o t o g r a p h y by R a i n e r e t a l . , (121) showed t h a t t h e r e was high frequency f l u t t e r i n g of the muscle-shelf l e a f l e t during e n d - s y s t o l e i n the a o r t i c Hancock valve. V e l o c i t y and s h e a r s t r e s s measurements c o n d u c t e d w i t h a s i z e 2 7 mm H a n c o c k s t a n d a r d v a l v e i n o u r l a b o r a t o r y g i v e r e s u l t s s i m i l a r to those obtained w i t h the Carpentier-Edwards valve (122). The v e l o c i t y p r o f i l e s were j e t - l i k e w i t h t u r b u l e n t s h e a r s t r e s s e s on t h e o r d e r o f 1000-3000 d y n e s / c m 2 , and w a l l s h e a r s t r e s s e s on the order of 200-600 dynes/cm2. F l o w s e p a r a t i o n was o b s e r v e d i n the immediate downstream v i c i n i t y o f the v a l v e , t o g e t h e r w i t h a region of stagnation adjacent to the outflow surfaces of the leaflets. L e a f l e t p h o t o g r a p h y s t u d i e s c o n d u c t e d by Yoganathan e t a l . , o n s i z e 2 7 a n d 2 5 mm H a n c o c k v a l v e s s h o w e d t h a t the l e a f l e t o p e n i n g a n d c l o s i n g c h a r a c t e r i s t i c s l e a v e much t o be desired (88). The l e a f l e t s d i d n o t open s y m m e t r i c a l l y o r reproducibly. The l e a f l e t o p e n i n g a r e a s v a r i e d w i t h c a r d i a c output. In t h e s t a n d a r d model Hancock v a l v e s t h e m u s c l e - s h e l f l e a f l e t was t h e l a s t o p e n a n d f i r s t t o c l o s e . The above observations are s i m i l a r to those observed with the CarpentierEdwards p o r c i n e v a l v e s , (d) Correlation The i n v i v o a n d i n v i t r o p r e s s u r e g r a d i e n t i n f o r m a t i o n c l e a r l y show t h a t t h e H a n c o c k p o r c i n e v a l v e s a r e m o d e r a t e l y t o h i g h l y s t e n o t i c , e s p e c i a l l y i n the s m a l l e r s i z e s . Patients with these v a l v e s w i l l n o t be a b l e t o l e a d v e r y a c t i v e l i v e s d u e t o t h e l a r g e g r a d i e n t s a c r o s s these v a l v e s under e x e r c i s e c o n d i t i o n s . The s t e n o t i c n a t u r e o f t h e v a l v e i s i n p a r t due t o t h e a s y m m e t r i c and i n a d e q u a t e o p e n i n g o f t h e t h r e e l e a f l e t s . The j e t type flow observed i n the flow v i s u a l i z a t i o n s t u d i e s could cause damage t o t h e a o r t i c o r v e n t r i c u l a r w a l l i f t h e j e t i m p i n g e s o n these w a l l s . As s t a t e d p r e v i o u s l y t h e v e l o c i t y and s h e a r f i e l d s



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downstream from the Hancock v a l v e s are q u i t e s i m i l a r t o those observed with Carpentier-Edwards valves (88,122). Therefore, s u b l e t h a l a n d / o r l e t h a l damage c o u l d o c c u r t o t h e e n d o t h e l i a l l i n i n g o f t h e v e s s e l w a l l s , r e d c e l l s , and p l a t e l e t s , w h i c h i n t u r n c o u l d l e a d t o h e m o l y t i c and t h r o m b o t i c p r o b l e m s . The o b s e r v a t i o n o f p l a t e l e t a g g r e g a t e s , f i b r i n t h r o m b i , and remnant p l a t e l e t s on t h e v a l v e l e a f l e t s s t r o n g l y s u p p o r t s the f a c t t h a t b l o o d e l e m e n t damage d o e s o c c u r . In a d d i t i o n , t h e f a c t t h a t p a t i e n t s w i t h H a n c o c k v a l v e s do e x p e r i e n c e t h r o m b o e m b o l i c and mild hemolytic problems a l s o s t r o n g l y suggests that red c e l l s and p l a t e l e t s a r e b e i n g damaged. The r e g i o n o f f l o w s e p a r a t i o n which e x i s t s a d j a c e n t to the downstream sewing r i n g , c o u l d l e a d t o t h e b u i l d up o f e x c e s s f i b r o u s t i s s u e a l o n g t h e downstream s e w i n g r i n g and t h e o u t f l o w bases o f t h e c u s p s . It could also l e a d t o t h e b u i l d up o f t h r o m b o t i c , f i b r o t i c a n d / o r calcific m a t e i r a l on t h e o u t f l o w s u r f a c e s o f t h e l e a f l e t s as o b s e r v e d by F e r r a n s e t a l . , ( 1 0 1 ) . We w o u l d a l s o l i k e t o p r o p o s e t h a t one o f t h e r e a s o n s f o r c a l c i f i c a t i o n i s the r e l a t i v e l y s t a g n a n t o r low v e l o c i t y r e g i o n o f f l o w t h a t e x i s t s between the outflow s u r f a c e s o f t h e l e a f l e t s and t h e v e s s e l w a l l s . The s t i f f n e s s o f t h e m u s c l e - s h e l f l e a f l e t makes i t s o u t f l o w s u r f a c e a p r i m e l o c a t i o n f o r the d e p o s i t i o n of thrombotic m a t e r i a l , f i b r o u s t i s s u e g r o w t h , and c a l c i u m b u i l d up.

6) St. Jude B i - L e a f l e t Valve i l Valve Description The S t . J u d e b i - l e a f l e t v a l v e i s a l o w p r o f i l e h e a r t valve prosthesis. T h e v a l v e i s made e n t i r e l y f r o m p y r o l y t i c c a r b o n w i t h a double v e l o u r Dacron sewing r i n g . The l e a f l e t s a r e p o s i t i o n e d w i t h i n t h e v a l v e h o u s i n g i n s u c h manner as t o p r o v i d e central flow. T h e l e a f l e t s p i v o t w i t h i n g r o o v e s made i n t h e v a l v e o r i f i c e housing. In the f u l l y open p o s i t i o n t h e l e a f l e t s a r e d e s i g n e d t o open an a n g l e o f 8 5 ° . The l e a f l e t s a r e i m p r e g n a t e d w i t h tungsten to improve t h e i r r a d i o - o p a c i t y , (b) In V i v o R e s u l t s The S t . J u d e p r o s t h e s i s has been o n c l i n i c a l t r i a l s and e v a l u a t i o n s s i n c e 1977, and was a p p r o v e d f o r g e n e r a l u s e i n D e c e m b e r , 1982. Over 2 0 , 0 0 0 o f t h e s e v a l v e s have been i m p l a n t e d t o date worldwide. The c l i n i c a l p r e s s u r e d r o p r e s u l t s i n d i c a t e t h a t t h i s v a l v e has p r o b a b l y t h e b e s t p r e s s u r e g r a d i e n t c h a r a c t e r i s t i c s o f any o f the p r o s t h e s e s i n c u r r e n t c l i n i c a l use. C a l c u l a t e c T V A ' s i n the a o r t i c p o s i t i o n have been i n the r a n g e o f 1 . 5 t o 3 . 6 c m 2 , and 2.1 t o 4 . 5 7 c m 2 i n t h e m i t r a l p o s i t i o n f o r s e w i n g r i n g s i z e s o f 21 t o 2 7 mm a n d 2 3 t o 31 mm, respectively. Even u n d e r e x e r c i s e c o n d i t i o n s t h e v a l v e has good pressure drop c h a r a c t e r i s t i c s . Blood d a t a on p a t i e n t s u s i n g t h i s p r o s t h e s i s i n d i c a t e t h a t the S t . Jude valve creates mild h e m o l y s i s i n most p a t i e n t s . Thromboembolic d a t a on the valve o v e r t h e p a s t t h r e e y e a r s t e n d t o i n d i c a t e a TEC r a t e o f a p p r o x i m a t e l y 1.0 to 2.0% per p t . y r . f o r p a t i e n t s on



YOGANATHAN ET AL.

Figure


6.

St.

Jude

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anticoagulation therapy (123-125). Without anticoagulation t h e r a p y t h e v a l v e w o u l d p r o b a b l y have an u n a c c e p t a b l y h i g h r a t e o f TEC e v e n t s . Due t o t h e s h o r t p e r i o d o f u s e o f t h i s p r o s t h e s i s no d e t a i l e d p a t h o l o g i c a l s t u d i e s o n r e c o v e r e d S t . J u d e v a l v e s have been r e p o r t e d i n t h e open l i t e r a t u r e . Recently t h e r e was a c a s e o f e x c e s s t i s s u e g r o w t h on t h e s e w i n g r i n g w h i c h p r e v e n t e d t h e o p e n i n g o f one l e a f l e t and a l l o w e d t h e s e c o n d l e a f l e t t o o n l y o p e n a b o u t h a l f way ( 8 8 ) . The valve was u s e d i n t h e a o r t i c p o s i t i o n and was r e c o v e r e d a t r e - o p e r a t i o n . T h e r e have been a few r e p o r t s i n t h e l i t e r a t u r e o f t h r o m b o s i s o f t h e S t . Jude v a l v e i n t h e a o r t i c , m i t r a l and t r i c u s p i d positions (126-128). Nunez e t a l . , r e p o r t e d two c a s e s w h e r e one l e a f l e t o f t h e S t . J u d e v a l v e was jammed by a v e r y small thrombus t h a t f i x e d the l e a f l e t i n a s e m i c l o s e d p o s i t i o n . Both p a t i e n t s were not a n t i c o a g u l a t e d . R e c e n t l y , we r e c o v e r e d a S t . J u d e a o r t i c v a l v e i n w h i c h b o t h l e a f l e t s w e r e jammed i n s e m i o p e n p o s i t i o n due t o t h r o m b i i n t h e v a l v e p i v o t m e c h a n i s m . M o u l t o n e t a l . , r e p o r t e d a c a s e w h e r e t h e t h r o m b u s was a d h e r e n t a t t h e j u n c t i o n o f t h e t w o l e a f l e t s a n d w h i c h e x t e n d e d 1 cm i n t o t h e a o r t a and t o t a l y o c c l u d e d t h e r i g h t c o r o n a r y o r i f i c e . The p a t i e n t was on a n t i c o a g u l a t i o n t h e r a p y . Ziemer et a l . , reported a c a s e o f i n t e r m i t t e n t i n h i b i t i o n o f l e a f l e t m o t i o n due t o m i n i m a l d i s p r o p o r t i o n between t h e l e a f l e t s and v a l v e r i n g ( 1 2 9 ) . (c) In V i t r o Results In v i t r o f l o w s t u d i e s i n d i c a t e t h a t t h i s v a l v e has t h e l o w e s t p r e s s u r e d r o p s o f any o f t h e p r o s t h e s e s i n c u r r e n t c l i n i c a l use. C a l c u l a t e d VA's were i n the range o f 1.4 t o 4 . 4 5 cm2 f o r the s i z e 1 9 t o 31 mm v a l v e s , i n b o t h a o r t i c a n d m i t r a l t e s t c h a m b e r s . A r e c e n t s t u d y by D e l l s p e r g e r e t a l . , ( 1 6 ) , however, indicates t h a t t h i s v a l v e may h a v e s i g n i f i c a n t r e g u r g i t a n t v o l u m e s a t low h e a r t r a t e s and low c a r d i a c o u t p u t s . For example, at a h e a r t r a t e o f 5 0 b e a t s / m i η t h e s i z e 2 7 mm S t . J u d e a o r t i c v a l v e had a t o t a l r e g u r g i t a n t volume o f 1 3 . 2 cnr/beat. Flow v i s u a l i z a t i o n s t u d i e s i n a o r t i c and m i t r a l chambers under b o t h s t e a d y and p u l s a t i l e f l o w i n d i c a t e smooth c e n t r a l type f l o w downstream from the v a l v e ( 4 8 , 8 5 , 8 8 , 1 3 0 ) . Initial v e l o c i t y a n d s h e a r s t r e s s m e a s u r e m e n t s h a v e b e e n made b y Y o g a n a t h a n e t a l . , w i t h s i z e 27 a n d 2 5 a o r t i c v a l v e s (38,131). T h e m e a s u r e m e n t s w e r e made u n d e r s t e a d y f l o w r a t e s o f 10 a n d 2 5 1/min. The v e l o c i t y m e a s u r e m e n t s i n d i c a t e t h a t t h e f l o w f i e l d t h a t emerges from the v a l v e i s c e n t r a l i z e d w i t h low t u r b u l e n c e intensities. The m e a s u r e m e n t s showed a r e g i o n o f f l o w s e p a r a t i o n i m m e d i a t e l y downstream from t h e s e w i n g r i n g and adjacent to flow channel w a l l s . The r e g i o n o f f l o w s e p a r a t i o n i s l a r g e r a d j a c e n t t o t h e c e n t e r o r i f i c e , compared t o the s e p a r a t i o n r e g i o n s a d j a c e n t t o t h e two s i d e o r i f i c e s . I t was a l s o o b s e r v e d t h a t t h e r e was more ( v o l u m e t r i c ) f l o w t h r o u g h t h e s i d e o r i f i c e s compared t o the c e n t e r o r i f i c e (approximate ratio of 70:30). W a l l s h e a r s t r e s s e s on t h e o r d e r o f 50 t o 600



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dynes/cm^ were measured t o g e t h e r w i t h e s t i m a t e d t u r b u l e n t shear s t r e s s e s of 100-600 dynes/cm2. V e l o c i t y measurements have n o t b e e n made c l o s e t o t h e p i v o t i n g m e c h a n i s m o f t h e v a l v e . Schramm e t a l . , u s i n g s t e a d y f l o w c o n d i t i o n s , have a l s o o b s e r v e d f l o w s e p a r a t i o n o c c u r r i n g from the downstream sewing r i n g (85). They s t a t e t h a t the f l o w s e p a r a t i o n g e n e r a t e s a c i r u c l a r dead water r e g i o n which surrounds the main f l o w . Studies i n our l a b o r a t o r y (88) and by R a i n e r e t a l . , (132) i n d i c a t e asynchronous c l o s i n g o f t h e two l e a f l e t s i n p u l s a t i l e f l o w . We h a v e a l s o observed that p a r t i c l e s of d i r t i n the blood analog f l u i d cause s t i c k i n g of the valve l e a f l e t s , (d) Correlation The i n v i v o and i n v i t r o r e s u l t s i n d i c a t e c l e a r l y t h e s u p e r i o r pressure drop c h a r a c t e r i s t i c s of the S t . Jude p r o s t h e s i s . T h i s i s a t r e m e n d o u s a d v a n t a g e f o r p a t i e n t s who l e a d a c t i v e l i v e s , as w e l l as f o r c h i l d r e n and a d u l t s w i t h s m a l l v a l v e a n n u l i (123-125). The r e g u r g i t a t i o n v o l u m e s o b s e r v e d J j i v i t r o a t low h e a r t r a t e s c o u l d be c l i n i c a l l y s i g n i f i c a n t a t l o w c a r d i a c outputs. One o f t h e r e a s o n s f o r t h i s r e s u l t c o u l d be t h e asynchronous c l o s i n g of the l e a f l e t s . The a s y n c h r o n o u s c l o s i n g o f t h e l e a f l e t s i s i n o u r o p i n i o n an i n h e r e n t p r o b l e m w i t h any bileaflet design, s i n c e o n e c a n n o t make b o t h l e a f l e t s identical. The c e n t r a l f l o w f i e l d c r e a t e d by t h e v a l v e i s an advantage. The w a l l s h e a r s c o u l d c a u s e s u b l e t h a l damage t o the e n d o t h e l i a l l i n i n g of the vessel w a l l s e s p e c i a l l y i n the a o r t i c p o s i t i o n , w h i l e the t u r b u l e n t shear s t r e s s e s could cause s u b l e t h a l a n d / o r l e t h a l damage t o b l o o d e l e m e n t s . It i s t h e r e f o r e n o t s u r p r i s i n g t o o b s e r v e m i l d h e m o l y s i s a n d TEC events, with this prosthesis. The r e g i o n o f f l o w s e p a r a t i o n c o u l d cause e x c e s s t i s s u e growth and/or thrombus f o r m a t i o n on the downstream sewing r i n g which i n t u r n c o u l d lead to valve d y s f u n c t i o n by i m p e d i n g movement o f t h e l e a f l e t s . This situation c o u l d be a g g r a v a t e d b y c e r t a i n s u r g i c a l t e c h n i q u e s s u c h a s u s i n g p l e d g e t s t o sew t h e v a l v e i n t o p l a c e . It is therefore of utmost i m p o r t a n c e t h a t t h e p h y s i c i a n be a b l e t o m o n i t o r t h e m o v e m e n t o f the l e a f l e t s under c i n e f l u o r o s c o p y . One o f t h e m a j o r c l i n i c a l disadvantages of the S t . Jude valve i s i t s poor r a d i o g r a p h i c v i s i b i l i t y , e s p e c i a l l y i f the p h y s i c i a n i s not f a m i l i a r w i t h the p r o s t h e s i s . The p r o b l e m o f s t i c k i n g l e a f l e t s as d o c u m e n t e d i n the medical l i t e r a t u r e , together w i t h our observations i n the p u l s e d u p l i c a t o r g i v e us c o n c e r n . A p o t e n t i a l f a i l u r e mode f o r t h i s p r o s t h e s i s c o u l d be damaged b l o o d e l e m e n t s c o l l e c t i n g i n t h e d i v e t s ( i . e . ears) of the hinge mechanism; forming small thrombi a n d c a u s i n g i m p a i r e d l e a f l e t m o b i l i t y , a s o b s e r v e d by us a n d other investigators.


142


Conclusions


F o l l o w i n g the c o l l e c t i o n , a n a l y s i s , and i n t e r p r e t a t i o n o f t h e i n v i v o and i n v i t r o i n f o r m a t i o n and d a t a p e r t a i n i n g t o the c u r r e n t s t a t e o f t h e a r t w i t h r e s p e c t t o t h e s a f e t y and p e r f o r m a n c e o f p r o s t h e t i c h e a r t v a l v e s ( m e c h a n i c a l and t i s s u e ) , we c o n c l u d e t h a t : 1.

A t p r e s e n t we d o n o t h a v e a n i d e a l p r o s t h e t i c h e a r t v a l v e . D u r i n g t h e p a s t 22 y e a r s , m a n u f a c t u r e r s h a v e d e v e l o p e d v a r i o u s d e s i g n s o f p r o s t h e t i c h e a r t v a l v e s , some o f w h i c h p e r f o r m s a t i s f a c t o r i l y when i m p l a n t e d s u r g i c a l l y i n p a t i e n t s s u f f e r i n g from v a l v u l a r heart d i s e a s e . O t h e r d e s i g n s have had t o be r e m o v e d f r o m t h e o p e n m a r k e t d u e t o l a c k o f adequate s a f e t y and e f f i c a c y .

2.

T h e r e i s a l a c k o f i n v i v o c l i n i c a l and i n v i t r o f l u i d d y n a m i c d a t a and i n f o r m a t i o n on a l l d e s i g n s o f p r o s t h e t i c heart valves in current c l i n i c a l use. The l a c k o f good q u a l i t y c l i n i c a l i n f o r m a t i o n and d a t a o n some o f t h e o l d e r valve types i s s u r p r i s i n g . Good, long term c l i n i c a l f o l l o w - u p data e x i s t s o n l y f o r the following valve types studied: (i) Starr-Edwards ball valves, (ii) Bjork-Shiley t i l t i n g disc valve, (iii) L i l l e h e i - K a s t e r t i l t i n g d i s c v a l v e , and ( i v ) Hancock p o r c i n e valve.

3.

4.

T h e r e i s a l a c k o f good d e t a i l e d p a t h o l o g i c s t u d i e s p e r f o r m e d on h e a r t v a l v e s p r o s t h e s e s r e c o v e r e d a t s u r g e r y and/or autopsy. The l a c k o f s u c h s t u d i e s w i l l h i n d e r t h e p r o g r e s s and d e v e l o p m e n t o f n o t o n l y b e t t e r h e a r t v a l v e p r o s t h e s e s , but a l s o o t h e r f u t u r e a r t i f i c i a l d e v i c e s such as l e f t v e n t r i c u l a r a s s i s t d e v i c e s and t h e t o t a l artificial heart.

5.

The c a l i b e r and q u a n t i t a t i v e n a t u r e o f t h e i n v i t r o f l u i d d y n a m i c s t u d i e s has i m p r o v e d a g r e a t d e a l d u r i n g t h e p a s t f i v e to s i x y e a r s . T h e r e a r e , h o w e v e r , many p i e c e s o f i n f o r m a t i o n m i s s i n g w h i c h w o u l d g i v e us a b e t t e r understanding o f some o f t h e c l i n i c a l p r o b l e m s o b s e r v e d w i t h p r o s t h e t i c heart valves. T h e r e s e e m s t o be a l a c k o f c o l l a b o r a t i o n b e t w e e n t h e i n v i t r o i n v e s t i g a t o r and t h e p h y s i c i a n ( c a r d i o l o g i s t a n d / o r cardiovascular surgeon). T h e r e f o r e , t h e r e a r e v e r y few a r t i c l e s that attempt to r e l a t e s p e c i f i c i n v i t r o flow c h a r a c t e r i s t i c s t o c l i n i c a l p e r f o r m a n c e and c o m p l i c a t i o n s . The l a c k o f s u c h i n f o r m a t i o n w i l l impede t h e p r o g r e s s o f p r o s t h e t i c h e a r t v a l v e s and s i m i l a r c a r d i o v a s c u l a r d e v i c e s . The a v a i l a b l e i n v i v o hemodynamic and i n v i t r o p r e s s u r e d r o p r e s u l t s f r o m aTT v a l v e s when a n a l y z e d i n a c o m b i n e d o v e r a l l m a n n e r i n d i c a t e t h a t t h e p r o s t h e s e s s t u d i e d c o u l d be arranged i n the f o l l o w i n g broad c a t e g o r i e s of d e c r e a s i n g s t e n o t i c i t y (The v a l v e s i n e a c h c a t e g o r y a r e l i s t e d i n alphabetical order): ( i ) caged d i s c v a l v e s ( i i ) caged

6.

7.


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b a l l v a l v e s , L i l l e h e i K a s t e r t i l t i n g d i s c v a l v e and p o r c i n e v a l v e s ( i i i ) B j o r k - S h i l e y t i l t i n g d i s c v a l v e and I o n e s c u Shiley p e r i c a r d i a l valve (iv) Medtronic-Hall t i l t i n g disc v a l v e (v) S t . Jude b i l e a f l e t v a l v e . 8.

In terms o f r e g u r g i t a t i o n , i n v i t r o s t u d i e s i n d i c a t e t h a t t h e v a l v e s c a n be a r r a n g e d i n t h e f o l l o w i n g b r o a d c a t e g o r i e s o f i n c r e a s i n g r e g u r g i t a t i o n (The v a l v e s i n e a c h c a t e g o r y a r e listed in alphabetical order): (i) porcine valves (ii) Ionescu-Shiley p e r i c a r d i a l valve ( i i i ) Beall disc valve, B r a u n w a l d - C u t t e r b a l l v a l v e , K a y - S h i l e y d i s c v a l v e , and Starr-Edwards ball valve (iv) Bjork-Shiley, Medtronic-Hall, and L i l l e h e i - K a s t e r t i l t i n g d i s c v a l v e s , and t h e S t . Jude bileaflet valve.

9.

A l l p r o s t h e t i c v a l v e s ( m e c h a n i c a l and t i s s u e ) i n c u r r e n t c l i n i c a l u s e c a u s e s u b l e t h a l a n d / o r l e t h a l damage t o b l o o d e l e m e n t s s u c h as r e d c e l l s and p l a t e l e t s . The s h e a r f i e l d s c r e a t e d by t h e v a l v e s ( 1 θ 2 - 1 θ 3 d y n e s / c m 2 ) a r e a l l c a p a b l e o f c a u s i n g s u c h damage. S u b l e t h a l damage t o r e d c e l l s c o u l d i n time lead to mild hemolysis. S i m i l a r l y , s u b l e t h a l damage to p l a t e l e t s could over a period of time lead to thromboemboli and T E C ' s .

10.

A l l p e r i p h e r a l f l o w t y p e v a l v e s c a u s e damage t o t h e e n d o t h e l i a l l i n i n g of the proximal ascending a o r t a . This i s d i r e c t l y r e l a t e d to the elevated wall shear s t r e s s e s (103 dynes/cm2) i n the immediate downstream v i c i n i t y o f these valves. T h e y may a l s o c a u s e s u b l e t h a l a n d / o r l e t h a l damage t o t h e v e n t r i c u l a r w a l l . Other mechanical valve d e s i g n s and t i s s u e b i o p r o s t h e s e s c o u l d c a u s e s u b l e t h a l a n d / o r l e t h a l damage t o t h e e n d o t h e l i a l l i n i n g o f t h e a o r t i c wall. The j e t t y p e f l o w f r o m t h e t i s s u e v a l v e s i n t h e a o r t i c and m i t r a l p o s i t i o n s c o u l d c a u s e damage t o t h e w a l l s o f t h e a s c e n d i n g a o r t a and l e f t ventricle, respectively. Depending on the o r i e n t a t i o n o f the v a l v e , the f l o w i n the major orifice region of a t i l t i n g disc mitral valve could also c a u s e damage t o t h e v e n t r i c u l a r w a l l .

11.

All prosthetic v a l v e s i n c u r r e n t c l i n i c a l use cause h e m o l y s i s and T E C ' s , and a r e p r o n e t o t h e p r o b l e m s o f throbmus f o r m a t i o n and e x c e s s t i s s u e g r o w t h on t h e valve superstructure. I n many c a s e s t h e h e m o l y s i s c a u s e d by t h e p r o s t h e s i s i s m i l d o r m o d e r a t e , and i s g e n e r a l l y compensated f o r q u i t e adequately by n a t u r a l r e g e n e r a t i o n i n t h e b o n e - m a r r o w . Cloth covering on the v a l v e s u p e r s t r u c t u r e (such as w i t h t h e S t a r r - E d w a r d s and B e a l l v a l v e s ) w i l l l e a d t o an i n c r e a s e i n h e m o l y s i s d e p e n d i n g on t h e s t r u c t u r e and s u r f a c e c h a r a c t e r i s t i c s o f the f a b r i c . H e m o l y s i s , however m i l d , i s not i n n o c u o u s . It i s the f o r e r u n n e r i n one o f t h e p r o p o s e d mechanisms f o r p l a t e l e t a g g r e g a t i o n and c o a g u l a t i o n , w h i c h i n t u r n c o u l d lead to the formation of thromboemboli.

12.


144 13.

14.


15.

16.


M e c h a n i c a l v a l v e s i n c u r r e n t c l i n i c a l u s e h a v e TEC r a t e s o f a b o u t 2 t o 8% p e r p t . y r . f o r p a t i e n t s o n a n t i c o a g u l a t i o n therapy. T i s s u e v a l v e s h a v e TEC r a t e s o f a b o u t 2 t o 5 . 5 % per p t . y r . w i t h o u t the use o f l o n g term a n t i c o a g u l a t i o n therapy. Thrombus f o r m a t i o n and t i s s u e o v e r g r o w t h on t h e v a l v e s u p e r s t r u c t u r e a r e most o f t e n found i n r e g i o n s o f f l o w s t a s i s , v e r y low f l o w and s h e a r , and f l o w s e p a r a t i o n . M e c h a n i c a l damage t o t h e b l o o d e l e m e n t s as w e l l as t o t h e e n d o t h e l i a l t i s s u e o f t h e a d j a c e n t v e s s e l w a l l , may i n a d d i t i o n t r i g g e r complex biochemical r e a c t i o n s which c o u l d l e a d t o the e x c e s s f i b r o u s t i s s u e o v e r g r o w t h o b s e r v e d on recovered valves. T i s s u e v a l v e s are prone to c a l c i f i c a t i o n , e s p e c i a l l y i n c h i l d r e n and young a d u l t s . C a l c i f i c a t i o n m a i n l y o c c u r s on the outflow surfaces of the l e a f l e t s . Therefore, it is very probable that the r e l a t i v e l y s t i f f nature of the current t i s s u e valve l e a f l e t s , together with the region of flow separation and/or flow stagnation which occurs between t h e o u t f l o w s u r f a c e s o f t h e l e a f l e t s and the v e s s e l w a l l , could lead to the deposition of c a l c i f i c , thrombotic and f i b r o t i c m a t e r i a l on t h e o u t f l o w s u r f a c e s .

Acknowledgments T h i s s t u d y was s u p p o r t e d (contract #223-81-5000).

by

the

Bureau

of

Medical

Devices,


FDA


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