Does it make sense to use two internal thoracic arteries?

D o e s It Make Sense to Use Two Internal Thoracic Arteries? Eric Berreklouw, MD, Jacques P. A. M. Sch6nberger, MD, PhD, Htisamettin Ercan, MD, Evert L. Koldewijn, MD, Marcel de Bock, MD, Victor J. Verwaal, MD, Frits van der Linden, MD, Ingeborg van der Tweel, PhD, Johannus H. Bavinck, MD, and Johan J. Bred6e, MD, PhD Department of Cardio-thoracic Surgery, Catharina Hospital, Eindhoven, the Netherlands

Retrospectively, the first 143 patients who were operated on with bilateral internal thoracic arteries (BITA group) were matched with 143 patients operated on with only one left internal thoracic artery anastomosed on the left anterior descending artery and additional ve in grafts (LITA group) and fol lowed up for a maximum of 8 years. At 5 years fol low-up there were no significant differences in event-free survival between the groups. After 8 years, the overall survival was 96% and 92% (not significant INS]), cardiac survival 99% and 97% (NS), angina-free cardiac survival 51% and 35% (NS), infarction-free cardiac survival 95% and 78% (NS), reintervention-free

cardiac survival 87% and 88% (NS), and all cardiac event-free survival 49% and 31% (NS) for the BITA and LITA groups, respectively. The incidence of late pulmonary, wound, and other complications was comparable. Cox proportional hazards analysis showed that a higher left ventricular end-diastolic pressure and female sex were predictors of recurrent angina and late cardiac events. During this intermediate-term follow-up, the use of one or two internal thoracic arteries was of no value in predicting angina-free or cardiac event-free survival.

(Ann Thorac Surg 1995;59:1456-63)

I t has been proved that the use of the left internal thoracic artery (LITA) anastomosed to the left anterior

descending artery (LAD) results in a better cardiac event- free and reoperation-free survival than the use of the saphenous vein as conduit to the LAD [1-4]. Few studies show that the use of both internal thoracic arteries (BITA) results in a better cardiac event-free survival than the use of the LITA only [4-7]. For patients aged 60 years or younger this incremental improvement might be more pronounced 16; Cosgrove DM, personal communication]. To achieve such an improvement in cardiac event-free and reoperation-free survival, one should question at what price this can be reached in terms of hospital mortality and morbidity and at what postoperative interval the expected improvement occurs. Recently we proved that the two internal thoracic arteries (ITA) can be used with similar hospital mortality and morbidity as with the use of only the LITA [8]. With this study, we want to answer the questions if the expected improvement in cardiac event-free survival occurred already within an intermediate term follow-up and if the use of one or two ITAs has an independen t predictive value in predicting late cardiac events in comparison with other preoperative and operative variables.

Accepted for publication Feb 17, 1995.

Address reprint requests to Dr Berreklouw, Department of Cardio- thoracic SurgeD,, Catharina Hospital, Michelangelolaan 2, 5602 ZA Eind- hoven, the Netherlands.

Mater ia l and M e t h o d s

Although more than 1,000 bilateral ITA operations have been performed in our center, we only studied retrospectively the first 143 hospital survivors with bilateral ITAs (BITA group) operated on between October 1985 and December 1988, and matched these survivors with 143 hospital survivors with only one LITA anastomosed on the LAD and additional vein grafts to other coronary arteries (LITA group). The patients were matched to the following criteria: time of operation (next consecutive patient), age, sex, and extent of coronary artery disease. Patients underwent BITA operation depending on pref- erence of the surgeon. All patients were operated on with pedicled ITAs as single or sequential grafts.

In the LITA group, the left ITA was anastomosed to the LAD, its branches, or both. In the BITA group, the left ITA was anastomosed to the LAD or its branches in 60.4% and to the circumflex coronary, artery or its branches in 39.6% of the patients. In BITA patients the right ITA was anastomosed to the LAD system in 37.7%, to the circumflex system in 30.4%, and to the right coronary artery and/or its branches in 31.9% of the patients. For the details of our operative techniques we refer to an earlier publication from our group [8]. Patients with free ITAs, gastroepiploic arteries, reoperations, or combined proce- dures were excluded from the study, as well as patients operated for an acute myocardial infarction. Complete- ness of revascularization was determined by computer analysis of the total n u m b e r of distal anastomoses di- vided by the n u m b e r of all coronary vessels that were

© 1995 by The Society of Thoracic Surgeons 0003-4975195159.50 0003-4975(95)00183-L

Ann Thorac Surg BERREKLOUW ET AL 1457 1995;59:1456-63 ONE OR TWO ITAs

Table 1. Preoperative Characteristics of the LITA and BITA Groups

LITA BITA Characteristics (n - 143) (n = 143) p Value

Age (yr) mean 54.9 (7.9) 53.9 (8.3) NS range 33-72 33-72

Male (%) 88.5 89.2 NS Angina

Class I (%) 2.9 2.9 Class I1 (%) 12.2 13.7 Class III (%) 54.7 44.6 NS Class IV (%) 23.0 31.7 Unstable (%) 6.5 7.2

Exercise ECG positive (%) 42.4 44.6 NS Exercise thallium positive (%) 10.8 8.6 NS Previous infarction (%) 54.7 54.7 NS Heart failure (%) 1.4 1.4 NS Hypertension (%) 36.0 33.4 NS Hyperlipidemia (%) 43.9 61.2 0.0039 Diabetes (%) 8.6 6.5 NS Smoking (%) 61.2 45.3 0.0082

Categorical data are presented as percentage of the total number of patients. Continuous data are presented as the mean with the standard deviation within parentheses.

BITA left and right ITA with or without vein grafts; LITA left [TA with vein grafts.

n a r r o w e d b y m o r e t h a n 50%. R e c u r r e n t a n g i n a was d e f i n e d as a n g i n a class 2 or m o r e d u r i n g fo l low-up . Ob jec t i ve i s c h e m i a at f o l l o w - u p was d e f i n e d as a pos i t i ve e l e c t r o c a r d i o g r a m (ECG) s t r e s s test. If a t h a l l i u m s t r e s s t es t was also done , t he r e s u l t of th i s t es t o v e r r u l e d t h e EC G s t re s s test . A n E C G s t ress t e s t or a t h a l l i u m s t ress t es t was p e r f o r m e d b y p r e f e r e n c e of t he r e f e r r i n g ca rd i - o logis t on a n e lec t ive bas is , for s y m p t o m s , or a c o m b i n a - t ion of t h e s e two.

Data Collection and Statistical Methods

All da ta w e r e c o m p i l e d in a c o m p u t e r i z e d d a t a b a n k a n d a n a l y z e d w i th the N u m b e r C r u n c h e r Sta t is t ica l S y s t e m (Hin tze , Kaysvi l le , UT) ( A p p e n d i x 1). S ta t i s t ica l ana lys i s of ca tegor ica l v a r i a b l e s was p e r f o r m e d o n c ro s s - t ab l e s u s i n g the P e a r s o n %2 test. C o n t i n u o u s v a r i a b l e s w e r e a n a l y z e d w i t h the t w o - s a m p l e t t es t if t he v a r i a n c e s of the g r o u p s w e r e equa l ; o t h e r w i s e t he M a n n - W h i t n e y U t e s t w a s used . Su rv iva l c u r v e s w e r e e s t i m a t e d w i t h t h e K a p l a n - M e i e r m e t h o d [9]. Di f fe rences of su rv iva l r a t e s b e t w e e n the two t r e a t m e n t g r o u p s w e r e a n a l y z e d by t h e log r a n k test . B ecause of t he smal l n u m b e r of p a t i e n t s at 8 yea r s fo l low-up , a c o m p a r i s o n also was m a d e of t h e c u m u l a t i v e su rv iva l p r o b a b i l i t y a f te r a 5 -yea r pe r iod . For e v e n t - f r e e su rv iva l ana lys is , e v e n t s w e r e d e f i n e d as all la te ca rd iac dea th s , n e w m y o c a r d i a l in fa rc t ions , r e c u r r e n t ang ina , a n d c o r o n a r y r e i n t e r v e n t i o n s ( c o r o n a r y a r t e ry b y p a s s g ra f t or p e r c u t a n e o u s t r a n s l u m i n a l c o r o n a r y an - g iop la s ty [PTCA]). For ana ly s i s of t he ca rd iac d e a t h - f r e e , a n g i n a - f r e e , r e in fa r c t i on - f r ee , c o r o n a r y r e i n t e r v e n t i o n -

Table 2. Preoperative Catheterization Data of the LITA and BITA Groups

LITA BITA Variables (n 143) (n = 143) p Value

Mainstem (%) 10.8 12.9 NS Left anterior descending (%) 95.0 96.4 NS Circumflex artery (%) 77.7 87.8 0.0263 Right coronary artery (%) 83.5 78.4 NS Number diseased coronaries 2.6 (0.7) 2.6 (0.5) NS LV end-diastolic pressure 12.5 (5.6) 13.5 (6.9) NS

(mm Hg)


BITA left and right ITA with or without vein grafts; LITA left ITA with vein grafts.

free, a n d e v e n t - f r e e surv iva l , on ly d e a t h a t t r i b u t a b l e to a ca rd iac cause was c o n s i d e r e d as mor ta l i ty . For ana ly s i s of p r e d i c t o r s for the a n g i n a - f r e e a n d e v e n t - f r e e su rv iva l t h e Cox p r o p o r t i o n a l h a z a r d s r e g r e s s i o n m o d e l [10] was used , u s i n g all da ta in p a t i e n t s w i t h a f o l l o w - u p of at l eas t 6 m o n t h s . To d e t e r m i n e t h e b e s t s u b s e t of p r ed i c to r s , a s e l ec t ion of v a r i a b l e s w a s m a d e b y M c H e n r y ' s a l g o r i t h m [11] f rom 22 p r e o p e r a t i v e a n d p e r o p e r a t i v e va r i ab le s , to w h i c h t h e t ype of ITA p r o c e d u r e w as a d d e d ( A p p e n d i x 2). R e g r e s s i o n ana lys i s w as t h e n p e r f o r m e d w i t h b a c k - w a r d e l i m i n a t i o n a n d was c o n t i n u e d un t i l all n o n s i g n i f - i can t p r e d i c t o r s w e r e r e m o v e d . In T a b l e 7 t h e re la t ive r isks a re ca l cu l a t ed f r o m t h e be t a e s t ima te s , w i t h 95% c o n f i d e n c e l imi ts u s i n g the s t a n d a r d e r r o r s of t he b e t a e s t ima tes . In all s ta t i s t ica l t es t s a t w o - s i d e d p v a l u e of less t h a n 0.05 w as c o n s i d e r e d to b e s igni f icant .

Results

Patient Matching

T h e p r e o p e r a t i v e cha rac t e r i s t i c s of t h e p a t i e n t s t h a t w e r e ava i l ab l e for f o l l o w - u p (Tab le 1) s h o w e d n o s ign i f i can t (NS) d i f f e rences in age, sex, p r e o p e r a t i v e a n g i n a class,

Table 3. Operative Data qf the LITA and BITA Groups

LITA BITA p Variables (n = 143) (n - 143) Value

Total number of distal anastomoses 3.2 (0.9) 3.3 (1.1) NS Number of ITA anastomoses 1.1 (0.3) 2.4 (0.6) Number of vein graft 2.1 (0.9) 1.0 (0.9)

anastomoses ITA, single graft (%) 90.6 69.8 ITA, jump graft (%) 9.4 30.2 No vein grafts (%) 0 33.8 Incomplete revascularization (%) 9.4 4.3 NS


BITA left and right ITA with or without vein grafts; LITA - left ITA with vein grafts.

1458 BERREKLOUW ET AL Ann Thorac Surg ONE OR TVVO ITAs 1995;59:1456-63

Table 4. Follow-up Data of the LITA and BITA Groups

LITA BITA p Variables (n = 136) (n 139) Value

Durat ion of follow-up (mo)

med ian 60.0 61.9 NS range t 0-93 1-95

Late overall mortali ty 9 (6.6) 5 (3.6) NS Late cardiac mortali ty 3 (2.2) 2 (1.4)

Angina class 1 117 (86.0) 121 (87.7) Angina class 2 11 (8.1) 12 (8.7) NS Angina class 3 8 (5.9) 5 (3.6) Angina class 4 0 0

Antianginal medicat ion 37 (27.2) 29 (20.9) NS Objective ischemia" 14 (11.3) 21 (17.4) NS New myocardial infarction 4 (2.9) 4 (2.9) NS Coronary re intervent ions 6 (4.4) 7 (5.0) NS Pulmonary complicat ions 4 (3.0) 5 (3.6) NS W o u n d complicat ions 6 (4.3) 8 (5.7) NS

Categorical data are presented as the actual numbers with the percentages within parentheses.

"~ Patients with tests only.


o b j e c t i v e i s c h e m i a , h e a r t f a i lu re , i n f a r c t i o n , h y p e r t e n - s ion , o r d i a b e t e s b e t w e e n s t u d y g r o u p s . BITA p a t i e n t s s m o k e d l e s s (45.3% v e r s u s 61.2%; p - 0.008), b u t h a d h y p e r l i p i d e m i a m o r e o f t e n (61.2% v e r s u s 43.9%; p - 0.004) t h a n t h e i r c o n t r o l LITA p a t i e n t s . A l t h o u g h t h e BITA g r o u p w a s m a t c h e d for t h e e x t e n t o f c o r o n a r y a r t e r y d i s e a s e , t h e c i r c u m f l e x a r t e r i e s w e r e m o r e in - v o l v e d in t h e s e p a t i e n t s t h a n in t h e LITA g r o u p (p = 0.026) (Tab le 2) Lef t v e n t r i c u l a r f u n c t i o n as e x p r e s s e d b y le f t v e n t r i c u l a r e n d - d i a s t o l i c p r e s s u r e w a s c o m p a r a b l e fo r b o t h s t u d y g r o u p s . A t o p e r a t i o n , t h e m e a n to ta l n u m b e r o f c o n s t r u c t e d d i s t a l a n a s t o m o s e s w a s s i m i l a r in

Table 5. Causes qf Death

Causes LITA BITA

Cardiac causes Heart failure 1 Myocardial infarction 1

Sudden death 1 U nknow n 1 1

Noncardiac causes Lung cancer 2 Pancreas cancer 1 Stomach cancer 1 Breast cancer 1 Gal lbladder cancer 1 Sigmoid cancer 1 Acute pancreati t is 1 Colitis ulcerosa 1 Total 9 5

BITA = both internal thoracic arteries w'ith or without vein grafts; LITA = left internal thoracic artery.

Table 6. Cumulative Percentage of Cardiac Survival of LITA and BITA Groups

P Survival LITA BITA Value

5-Year Overall survival 93.8 (2.6) 96.2 (1.7) NS Cardiac death- f ree ~ 98.5 (1.1) 98.6 (1.0) NS Angina- f lee and 95.0 (2.1) 96.7 (1.6) NS

alive a Infarction-free and 97.5 (1.5) 97.6 (1.4) NS

alive a Reintervent ion-free 94.5 (2.3) 97.7 (1.4) NS

and alive "~ All cardiac event- f ree 93.1 (2.6) 95.0 (2.0) NS

(as defined) a 8-Year

Overall survival 92.3 (2.6) 96.2 (1.7) NS Cardiac death- f ree a 97.0 (1.9) 98.5 (1.0) NS Angina-f ree and 35.1 (16.1) 51.4 (13.5) NS

alive "~ Infarct ion-free and 77.8 (10.6) 95.1 (2.2) NS

alive ~ Reintervent ion-f ree 88.2 (4.0) 87.1 (5.7) NS

and alive ~ All cardiac event- f ree 31.3 (14.6) 48.6 (12.8) NS

(as defined) a

Data are presented as percentages with standard error within parentheses.

'~ Noncardiac deaths excluded.


b o t h g r o u p s . B e c a u s e of t h e s t u d y d e s i g n , t h e r e w e r e m o r e a n a s t o m o s e s p e r f o r m e d w i t h v e i n g r a f t s in t h e LITA g r o u p , w h e r e a s in BITA p a t i e n t s t h i s w a s d o n e m o r e o f t e n w i t h t h e ITAs (Tab le 3). I n 47 BITA p a t i e n t s n o v e i n s w e r e u s e d ( c o m p l e t e a r t e r i a l r e v a s c u l a r i z a t i o n ) .

Overall Survival

O f t h e 286 p a t i e n t s w h o w e r e m a t c h e d , 2 p a t i e n t s (0.7%) d i e d w i t h i n 30 d a y s of h o s p i t a l i z a t i o n a n d o f t h e r e m a i n -

% 100

80

60

4Q

20

0

Log Rank t e s t NS

i ~ [ l e n [ s 8 t r i sk

136 131 121 112 47 8 lira

I I I I I I I I I I I I I I I I I I I I I I f 8 16 24 32 40 48 56 64 72 80 88

4 12 20 28 36 44 52 60 68 76 84 92

months

lita bita

Fig 1. Overall survival estimates for left internal thoracic artery (lita) and bilateral internal thoracic arteries (bita) patient groups. (NS = not significant.)


% 1 0 0

8O

6 0

i 4 0 1

2 0

0

136 13~ 121 112 47 8 lira

L I I I I L I I I I , L ! L I I I I I I { I I 8 1 6 2 4 3 2 4 0 4 8 5 6 6 4 7 2 8 0 8 8

4 1 2 2 0 2 8 3 6 4 4 5 2 6 0 6 8 7 6 8 4 9 2

months

l i ta b i t a

Fig 2. Cardiac survival estimates for lift internal thoracic artery (lita) and bilateral internal thoracic arteries Poita) patient groups. (NS = not significant.)

% 1 0 0

L ~ R ~ NS " ' ' " ' % ' - - ~

6O

4 0 " ~ " paD~[its ~1 risk - , . . . . . . . .

139 133 125 118 61 12 bita 2 0

136 13] 121 112 '17 a li(a

0 I L I I I I I I i I L I I I I I I q l t I I 8 1 6 2 4 3 2 4 0 4 8 5 6 6 4 7 2 8 0 8 8

4 1 2 2 0 2 8 3 6 4 4 5 2 6 0 6 8 7 6 8 4 9 2

months

l i ta b i t a

Fig 3. Angina-free cardiac survival estimates for left inter~al thoracic artery (lita) and bilateral internal thoracic arteries (bita) patient groups. (NS = not significant.)

ing pat ients , 9 (3.1%) w e r e lost to fo l low-up. The m e d i a n dura t ion of fo l low-up was c o m p a r a b l e for bo th g roups (Table 4). N i n e pa t ien ts (6.6%) in the LITA group and 5 pa t ien ts (3.6%) in the BITA group d ied dur ing fo l low-up (Table 5). At 5 and 8 years, the overal l survival of BITA and LITA pat ien ts was not s ignif icant ly different (Table 6). The overal l surv iva l curves dur ing 8 years of fo l low-up w e r e s imilar (Fig 1). The n u m b e r of dea ths was too small to a l low a mul t iva r ia te analysis of predic tors for late mortal i ty .

Cardiac S u r v i v a l

There w e r e only three late cardiac dea ths (2.2%) in the LITA group and two (1.4%) in the BITA group (see Tables 4, 5). The 5- and 8-year cardiac dea th - f ree survival (see Table 6) and cardiac survival curves were s imilar for bo th g roups (Fig 2).

R e c u r r e n t l s c h e m i a

In 19 (14%) of the LITA and 17 (12.3%) of the BITA pat ien ts angina r e c u r r e d (NS) (see Table 4). A l t h o u g h the ang ina - f r ee cardiac survival at 5 and 8 years was s imilar

for bo th g roups (see Table 6), the ang ina - f r ee cardiac survival at the e n d of fo l low-up was 51% (s tandard er ror [SE] 13.5) for the BITA and 35% (SE 16.1) for the LITA groups (NS) (Fig 3). Cox p ropor t iona l haza rds analysis s h o w e d that f emale sex (p = 0.009) and a h i g h e r left ven t r i cu la r end-d ias to l ic p re s su re (p = 0.038) had p red ic - t ive va lue for the occur rence of late ang ina (Table 7). E leven of 31 (35.5%) w o m e n ve r sus 25 of 244 (10.2%) m e n had r ecu r ren t ang ina at fo l low-up (p < 0.001). The use of one or two ITAs did not in f luence overa l l ang ina - f r ee survival . An exercise ECG test was p e r f o r m e d in 115 LITA and 118 BITA pat ients . An exercise tha l l i um test was done in 18 LITA and 15 BITA pat ients . Objec t ive i schemia was shown in 17.4% of the BITA and 11.3% of the LITA pa t ien ts (NS) (see Table 4). Of all pa t ien ts w i thou t r ecu r ren t angina , the re w e r e 18 pa t ien ts w h o s h o w e d a pos i t ive exercise ECG, w h e r e a s of all pa t ien ts wi th r ecu r r en t angina , the re w e r e also 18 pa t ien ts w h o s h o w e d a nega t ive exercise ECG. Four pa t ien ts in bo th g roups sus t a ined a n e w myocard ia l infarc t ion (NS). At 5 years, 97.5% of the LITA and 97.6% of the BITA pat ien ts were infarct free (NS) (see Table 6). The infarc t - f ree

Table 7. Predictors for Late Cardiac Events

Beta Standard Chi-square p Value Relative Confidence Predictors Estimate Error (Beta = 0) (Beta = 0) Risk Limits (95%)

Predictors for late angina" (37 patients with events)

Female sex 0.9613 0.3694 6.77 0.0093 2.6 (1.3-5.4) LVEDP 0.0525 0.0253 4.32 0.0378 1.1 (1.0-1.1) One or two ITAs 2.71 (NS)

Predictors for all late cardiac events" (45 patients with events) LVEDP 0.0487 0.0222 4.83 0.0280 1.1 (1.0 -1.1) Female sex 0.7201 0.3545 4.13 0.0422 2.1 (1.0-4.1) One or two ITAs 1.81 (NS)

"~ Noncardiac deaths excluded.

ITA = internal thoracic artery; LVEDP = left ventricular end-diastolic pressure; NS = not significant.

1460 B E R R E K L O U W ET AL Ann Thorac Surg ONE OR TWO |TAs 1995;59:1456-63

% 1 O0

Leg Raok test NS

80

60

4 0 patlen[s al r sk

20 el " - 139 133 125 118 12 ulta

136 131 121 112 47 8 lita

I I I I I I I I I I I I i I I I I I I ~ I I

0 8 16 24 32 4 0 4 8 56 6 4 72 8 0 8 8

4 12 20 28 3 6 4 4 52 6 0 68 76 8 4 92

months

l i ra b i ta

Fig 4. Infarct-free cardiac survival estimates for left internal thoracic artery (lita) and bilateral internal thoracic arteries (bita) patient groups. (INS = not significant.)

% 1 0 0

8 0 l- g R kl l~'IS

60

40 • -

palieTitg at r i sk

20 139 ]J3 - ,~25- 1] 8 6] " . . 1 ~ 6,t~l " .

136 131 121 112 47 8 lira

0 I I I I I I I I i I I I i I I l I I I I I I I I

0 8 16 2 4 32 4 0 48 56 6 4 72 8 0 88

4 12 20 2 8 3 6 44 52 6 0 68 7 6 8 4 92

months

l i ra b i ta

Fig 6. Event-free cardiac survival estimates for left internal thoracic artery (lita) and bilateral internal thoracic arteries (bita) patient groups. (NS = not significant.)

cardiac survival curves, over the 8-year period, were similar for both groups (Fig 4).

C o r o n a r y R e i n t e r v e n t i o n s

Six (4.4%) of the LITA and 7 (5.0%) of the BITA patients underwent a coronary reintervention (NS) (see Table 4). In 6 LITA patients PTCA was performed eight times. In 7 BITA survivors PTCA was performed eight times and in 1 patient, thrombolysis. The reason for the reinterven- tions was progression of disease in the native circulation in all patients. In none of the patients a coronary bypass reoperation had to be performed. At 5 years, 97.7% of the BITA and 94.5% of the LITA patients were reintervention free (NS) (see Table 6). The reintervention-free cardiac survival curves were similar for both groups (Fig 5).

E v e n t - f r e e S u r v i v a l

At 5 years, 95.0% of the BITA and 93.1% of the LITA patients were free of a cardiac event (NS) (see Table 6). At 92 months the cardiac event-flee survival was 49% for

% 1 0 0

Log Rank test NS " . ........... ~ . . . . . . . . . . . . . . . . . . .

8O

6O

4 0

pabenls al r,sk

20 1 3 9 133 125 ]18 61 12 [31ta

,36 ~3~ ~2~ ,2 47 ~ ,,io 0 I I I I I I I I P I I I I I I I I I I I

0 8 16 24 32 4 0 4 8 56 6 4 72 8 0 8 8

4 12 20 28 36 4 4 52 60 68 76 8 4 92

months

l i ta b i ta

Fig 5. Reinterventton-free cardiac survival estimates for left internal thoracic artery (lita) and bilateral internal thoracic arteries (bita) patient groups. (NS = not significant.)

BITA and 31% for LITA patients (NS) (Fig 6). Cox proportional hazards analysis showed that predictors for a late cardiac event were a higher left ventricular end- diastolic pressure (p = 0.028) and female sex (p = 0.042) (see Table 7). The use of one or two ITAs had no predictive value for late cardiac event-free survival.

O t h e r L a t e C o m p l i c a t i o n s

In 4 LITA patients (3.0%) and 5 BITA patients (3.6%) pu lmonary problems, such as pleural effusions and pneumonia , were observed (NS) (see Table 4). Six LITA patients (4.3%) and 8 BITA patients (5.7%) sustained wound problems (NS). Of these, 1 BITA patient had mediastinitis and 3 BITA patients had a superficial infection of the chest wound. Four LITA patients had an infection of the leg wound and 1 LITA patient had a superficial chest wound infection. Nineteen LITA patients (11.8%) and 16 BITA patients (11.5%) sustained other late complications or diseases during follow-up. Of these, 9 BITA patients (6.5%) and 3 LITA patients (2.2%) sustained a cerebral t ransient ischemic attack or vascular accident during follow-up.

C o m m e n t

The long-term survival and relief of angina and infarction after a coronary bypass operation are related to the preoperative status of the patient, progression of coronary artery sclerosis, and patency of the conduits used [12]. The patency of an internal thoracic artery graft 5 to 12 years after the operation is superior to that of saphenous vein grafts, being 97% versus 46%, respectively [13]. In retrospective [1-4] and prospective [14] studies it has been shown that the use of the LITA, instead of the saphenous vein, anastomosed to the LAD results in a significantly better cardiac event-free survival. There are only a few studies that compare the late results after the use of one versus two ITAs [4-7]. Cameron and colleagues [4] (38 BITA patients) and Cosgrove and colleagues [6; personal communication] (327 BITA patients)


did not apply their statistics on the compar ison of two versus one ITA, but to the tr iple compar ison with a no ITA group as well. Only Fiore [5l and Naunhe im [7] and their colleagues compared 100 BITA pat ients with a similar group of LITA patients, as in our study. One should be cautious to compare our s tudy with these other studies. Not only are there differences in s tudy design and pat ient populat ions, but there are also differences in the t ime frame of the operat ions, in the dura t ion of follow-up, in operat ive techniques, in percentage of incomplete revascularization, and in myocardia l preserva- tion techniques used. Cameron and associates [4] did not per form sequent ia l grafts with their ITAs and opera ted on a fibril lating heart. Fiore [5] and Naunhe im [7] and their co-workers per formed only single ITA anastomoses, placing the left ITA always on the LAD and the right ITA always on the right coronary artery. We demons t ra ted that the overall survival for hospital survivors after 92 months was comparable for the BITA (96%) and LITA groups (92%) (NS). Naunhe im and colleagues [7l failed to show a significant benefit in survival ( including the hospital mortality), over a 15-year per iod of pat ients in which they used two versus one ITA. Cosgrove and colleagues [6; personal communicat ion[, excluding the hospital mortality, could not demons t ra te a significantly bet ter 8-year survival for two ITAs in pat ients older than 60 years of age. Only in pat ients younger than 60 years of age did they demonst ra te a significantly bet ter survival after BITA operat ion. The number of late deaths in our s tudy was too small to allow for an analysis of predictors for these incidents. Sergeant and associates [15] could not demonst ra te in a mult ivariate analysis any addi t ional benefit on late survival with the addi t ional use of the right ITA. But this could be due to the fact that they used exclusively the right ITA on the diagonal branch, adding not much to the effect of the LITA on the LAD.

We could not demons t ra te any significant difference in late cardiac mortal i ty be tween the s tudied groups, being 1% in the BITA and 3% in the LITA group. Several investigators [1, 151 have shown that the use of the LITA to bypass a LAD lesion is an impor tant predic tor of cardiac survival. It is l ikely that in an 8-year per iod the addi t ional use of the right ITA on another vessel does not affect cardiac survival.

We found no significant difference in angina-free cardiac survival after 92 months in our BITA (51%) and LITA (35%) patients. Cameron and colleagues [4] found 68% of their BITA patients and 52% of their LITA pat ients free of recurrent angina after a follow-up of 13 years. Fiore and associates [5] showed a significantly bet ter recurrent angina-free survival for BITA (36%) than for LITA (27%) pat ients after a follow-up of 15 years. Al though the use of one ITA does not appear to have much effect on recurrent angina [12], it is l ikely that the use of a second ITA does. In our mult ivariate analysis, we found female sex and a h igher left ventr icular function as predictors for recurrent angina. Also Sergeant and associates [16] showed in their Cox hazards analysis that these same variables, among others, were risk factors for angina after the operation.

The incidence of late myocardia l infarctions in our

s tudy was low and not different be tween the s tudied groups. Fiore and colleagues [5] found no difference in myocardia l infarction after one or two ITAs in the first 10 years of follow-up, but at 15 years 75% of the BITA and 59% of the LITA pat ients were infarction free. Therefore, it is l ikely that dur ing the first 8 to 10 years there is no difference in recurrent infarction be tween one or two ITAs, but that after that t ime the curves diverge.

After 92 months, 87% of the BITA and 88% of our LITA patients d id not need a coronary ar tery reintervention. All re intervent ions in our pat ients were for PTCA. Cam- eron [4] and Fiore [5] and their associates did show that the incidence of reopera t ion was the lowest for BITA patients at 15 years ' follow-up.

After 8 years, we demonstrated a cardiac event-free survival for BITA patients of 49% and for LITA patients of 31% (NS). Because of the small number of patients remain- ing on study at 8 years, the 49% versus 31% comparison should not yet be interpreted as being suggestive of a trend. Cameron and colleagues [4] found a cardiac event-free survival of 48% with BITA and 27% with LITA patients after 14 years of follow-up. During the first 8 years, Fiore and colleagues [5] also could not demonstrate a difference in ischemic events between LITA and BITA patients. How- ever, after 8 years, the curves diverged. Thirty-two percent of the BITA patients and 18% of the LITA patients were ischemic events-free at a follow-up of 15 years, which was significantly different. We found that left ventricular pressure and female sex were predictors for late cardiac events, and not the fact that one or two ITAs were used. Cosgrove and colleagues [6; personal communication[ found age, the use of one ITA, a history of heart failure, and diabetes were such predictors. In patients younger than 60 years of age, they also found left ventricular function and sex as predictors.

In summary, we demons t ra ted earl ier that a BITA operat ion can be done with comparable hospi tal mortality and morbid i ty as an LITA operat ion [81. With this study, we also showed that, at in te rmedia te - te rm follow- up, the event-free survival of a BITA opera t ion is comparable to that of using only the LITA. Al though the use of one or two ITAs has no predict ive value for the angina-free and event-free survival dur ing the first 8 years after operat ion, such a pat ient should not be denied the use of both ITAs if this pat ient is to be expected to survive beyond these 8 to 10 years postoperat ively, espe- cially if such a pat ient is younger than 60 years of age, a l though such difference for the age groups has to be confirmed.

R e f e r e n c e s

1. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery on 10-year survival and other cardiac events. N Engl J Med 1986;314:1-6,

2. Okies JE, Page US, Bigelow JC, et al. The left internal mammary artery: the graft of choice. Circulation 1984; 70(Suppl 1):213-21.

3. Killen DA, Arnold M, McConahay DR, et al. Fifteen-year results of coronary artery bypass for isolated left anterior descending coronary artery disease. Ann Thorac Surg 1989; 47:595-9.

1462 BERREKLOUW ET AL Ann Thorac Surg ONE OR TWO ITAs 1995;59:1456-63

4. C a m e r o n A, K e m p HG, Green GE. Bypass su rge ry with the in te rna l m a m m a r y ar tery graft: 15 year fol low-up. Circula- t ion 1986;74(Suppl 3):30-6.

5. Fiore AC, N a u n h e i m KS, D e a n P, et al. Resul t s of in ternal thoracic ar tery graf t ing over 15 years: s ingle ve r su s double grafts. A n n Thorac Surg 1990;49:202-9.

6. Cosgrove DM, Hill A, Lytle BW, et al. Are two in ternal thoracic ar ter ies be t ter t han one? P re sen t ed at the 72nd A n n u a l M e e t i n g of The Amer i can Associa t ion for Thoracic Surgery, Los Angeles , CA, April 27-29, 1992.

7. N a u n h e i m KS, Barner HB, Fiore AC. Resul ts of in ternal thoracic ar tery graf t ing over 15 years: s ingle ve r su s double grafts; 1992 upda te . A n n Thorac Surg 1992;53:716-8.

8. Ber rek louw E, SchBnberger JPAM, Bavinck JH, et al. Similar hospi ta l morb id i ty with the use of one or two in ternal thoracic arteries. A n n Thorac Surg 1994;57:1564-72.

9. Kap lan EL, Meier P. N o n p a r a m e t r i c es t imat ion f rom incomplete observa t ions . J A m Stat Assoc 1958;53:457-61.

10. Cox DR. Regress ion m o d e l s and life-tables. J R Stat Soc 1972;34:187.

11. M c H e n r y CE. C o m p u t a t i o n of a bes t s u b s e t in mul t ivar ia te analysis . J R Stat Soc, Series C 1978;27:291-6.

12. Gould BL, Clayton PD, J ensen RL, et al. Associa t ion b e t w e e n ear ly graft pa tency and late ou t come for pa t i en t s u n d e r g o i n g ar tery b y p a s s graft surgery . Circulat ion 1984;3:.569-76.

13. Lytle BW, Loop FD, Cosgrove DM, et al. L o n g - t e r m (5-12 years) serial s tud ies of in terna l m a m m a r y ar tery and s ap h e - nous ve in coronary b y p a s s grafts. J Thorac Card iovasc Surg 1985;89:248 -58.

14. Zeff RH, K o n g t a h w o r n C, l a n n o n e LA, et al. In ternal m a m - mary artery, v e r s u s s a p h e n o u s ve in graft to the left anter ior d e s c e n d i n g coronary artery: prospec t ive r a n d o m i z e d s t u d y with 10-years fol low-up. A n n Thorac Surg 1988;45:533-6.

15. Sergean t P, Lesaffre E, F l ameng W, et al. In terna l m a m m a r y artery: m e t h o d s of use and their effect on surv iva l after coronary b y p a s s surgery . Eur J Card io thorac Surg 1990;4: 72-8.

16. Se rgean t P, Lesaffre E, F l a m e n g W, et al. The re tu rn of clinically ev iden t i s chemia after coronary ar tery b y p as s graft ing. Eur J Card io thorac Surg 1991;5:447-57.

Appendix 1. Listing ql: Coded Variables

Variable Code

Sex 0 male 1 female

Age (y) A n g i n a class 1 -4 (Canad ian classification) History, of hear t failure 0 none

1 - yes Prev ious myocard ia l 0 = none

infarctiori 1 yes Smok ing 0 - none

1 yes Diabetes mel l i tus 0 none

1 yes, insu l in 2 yes, oral medica t ion

H y p e r t e n s i o n 0 none 1 yes

Hyper l ip idemia 0 n o n e 1 hype rcho le s t e ro l emia 2 hyper t r ig lyce r idemia

Exercise ECG 0 not done 1 posit ive 2 nega t ive

Exercise tha l l ium 0 - not done 1 - posit ive 2 nega t ive

N u m b e r of d i seased 1 - main s t e m coronary s y s t e m s 2 = two sys t ems , o ther than

ma in 3 three svs t ems , o ther

than ma ih N u m b e r of d i seased (n)

coronary ar ter ies Left ven t r icu la r end-dias to l ic (ram Hg)

p r e s su re Date of opera t ion date Type of p rocedure I - LITA single ÷ vein

2 LITA j u m p + vein 3 -- BITA single + vein 4 = BITA single, no vein 5 - BITA j u m p + vein 6 - BITA jump, no vein

Surgeon 1-5 One or two ITAs I :- one

2 two

Appendix 1. Continued

Variable Code

Total n u m b e r of distal 2 -6 a n a s t o m o s e s

N u m b e r of ITA a n a s t o m o s e s 1 -4

N u m b e r of vein 0 -3 a n a s t o m o s e s

C o m p l e t e n e s s of 1 = comple te revascular iza t ion 2 = incomple te

Date of last fol low-up date Interval after opera t ion in m o n t h s Late ang ina class 1 -4 (Canad ian classification) Late an t i ang ina l med ica t ion 0 none

1 = yes Late exercise ECG 0 not done

1 posi t ive 2 - nega t ive

Late exercise tha l l ium 0 - no t done

1 posit ive 2 nega t ive

Late lung compl ica t ions 0 none

1 = effusion with punc t ion 2 p n e u m o n i a 3 - pleur i t is exsuda t iva

Late w o u n d compl ica t ions 0 none 1 s u b c u t a n e o u s infection

s t e r n u m 2 s t e r n u m deh i scence 3 ~ medias t in i t i s 4 infect ion leg w o u n d

Late myocard ia l infarct ion 0 none 1 - yes

Mortal i ty 0 none 1 opera t ive 2 -- hospi ta l 3 after 30 days

Late coronarv 0 none r e in t e rvenf ions 1 - PTCA

2 re -CABG 3 th rombolys i s

BKI-A : bilateral ITA; CABG coronary artery bypass grafting; ITA internal thoracic artery; LITA percutaneous transluminal corona r)~ angioplasty.


Appendix 2. Variables Considered as Independent Variables in the Cox Proportional Regression Analysis

Preoperative variables Age Sex Angina class History of heart failure Previous myocardial infarction Smoking Hypertension Hyperlipidemia Diabetes Exercise ECG Exercise thallium Number diseased coronary arteries Main disease Left anterior descending coronary artery disease Circumflex coronary artery disease Right coronary artery disease Left ventricular end-diastolic pressure

Operation-related variables Total number of distal anastomoses Number of internal thoracic arteries-distal anastomoses Number of veins--distal anastomoses Completeness of revascularization Surgeon One or two internal thoracic arteries

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