Comparative analysis of mechanical and bioprosthetic valves after aortic valve replacement

J

THORAC CARDIOVASC SURG

1987;94:20-33

Comparative analysis of mechanical and bioprosthetic valves after aortic valve replacement Comparative long-term pedormance characteristics of Bjork-Sbiley mechanical and bioprosthetic valves were analyzed for patients undergoing aortic valve replacement between 1976 and 1981. A total of 419 patients received either a standard Bjork-Sbiley (n = 266) or bioprosthetic (porcine, n = 126, or pericardial, n = 27) aortic valve. Cumulative patient foUow-up was 1,705 patient-years; the average patient foUow-up was 4.1 ± 2.7 years. Survival data were obtained for aU but 11 patients (97% complete foUow-up) up to 9 years after operation. Survival at 5 years was 81 % ± 4 % (± standard error) for Bjork-Sbiley and for bioprost:JIetic valve recipients. Valve failure in the Bjork-Sbiley group was predominately due to valve-related mortality and did not result from structural failure. Patients with bioprosthetic valves experienced valve failure as a result of prosthetic valve endocarditis and intrinsic valve degeneration. Althougll patients with bioprostheses experienced a lower incidence of valve-related morbidity than Bjork-Sbiley valve recipients (p < 0.03), no difference could be demonstrated in the incidence of valve-related mortality or valve failure at 5 years between bioprosthetic and Bjork-Sbiley valves. Mortality rate from valve failure was higher for Bjork-Sbiley (86%, 12/14) than bioprosthetic valves (36%, 5/14) (p < 0.01).

A. Michael Borkon, M.D., Lisa M. Soule, M.A., Kenneth L. Baughman, M.D., Hacib Aoun, M.D., William A. Baumgartner, M.D., Timothy J. Gardner, M.D., Levi Watkins, Jr., M.D., Vincent L. Gott, M.D., and Bruce A. Reitz, M.D., Baltimore, Md.

Although comparisons may be made of single valve studies from various institutions, differences in operative techniques, patient populations, modes of follow-up, and time frames of analysis may obscure determination of the most favorable prosthesis.' To avoid these deficiencies, we conducted this study to compare mechanical, Bjork-Shiley, and bioprosthetic valves implanted during a coincident 5 year period between 1976 and 1981. Computation of valve-related events and use of a comprehensive definition of valve failure were employed to permit analysis of cardiac valve substitutes with distinctly different attributes and modes of valve failure. From the Divisionof Cardiac Surgery and Cardiology, Johns Hopkins Hospital, Baltimore, Md. Computational assistance received from Clinfo, National Institutes of Health Grant RR-00035. Read at the Twelfth Annual Meeting of The Western Thoracic Surgical Association, Napa, Calif., June 25-29, 1986. Address for reprints: A. Michael Borkon, M.D., Johns Hopkins Hospital, Divisionof Cardiac Surgery, Blalock 618, 600 N. Wolfe St., Baltimore, Md. 21205.

20

Patients and material Between January 1976 and December 1981, 419 nonconsecutive adult patients underwent aortic valve replacement with either a Bjork-Shiley standard spherical disc (n = 266) or a bioprosthetic (n = 153) valve. Bioprosthetic valves inserted during this period included Ionescu-Shiley (27), Carpentier-Edwards (37), and Hancock (89) models. To determine 'and compare specific valve-related complications, we excluded from this analysis patients receiving multiple valve replacements. Patients undergoing concomitant operations such as coronary artery bypass or ascending aortic resection were included. Valve selection was determined arbitrarily by individual surgeon preference. The preoperative clinical characteristics of patients receiving Bjork-Shiley and bioprosthetic valves are listed in Table I. The two groups were essentially similar except for a significantly increased duration of cardiopulmonary bypass and total myocardial ischemia among Bjork-Shiley than bioprosthesis recipients. Also, there were more small-sized aortic valves « 21 mm) in the Bjork-Shiley group (118/266, 44%) than the bioprosthesis group (16/153, 11%) (p < 0.001). Nevertheless,

Volume 94 Number 1 July 1987

Aortic valve replacement

21

Table I. Preoperative clinical characteristics No. of patients Mean age (yr) Male/female ratio Angina pectoris (%) Previous myocardial infarction (%) NYHA (CHF) Class III or IV (%) Previous aortic valve replacement (%) Endocarditis (%) Atrial fibrillation (%) Cardiothoracic ratio (%) PA mean pressure (mm Hg) Cardiac index (Lyrnin/m") L VEDP (mm Hg) Ejection fraction (%) Predominant hemodynamic lesion Aortic stenosis (%) Aortic regurgitation (%) Mixed stenosis/regurgitation (%) Other (%) Concomitant procedure Coronary artery bypass (%) Aortic aneurysm resection (%) Cardiopulmonary bypass (min) Aortic cross-clamp time (min)

Bjork-Shiley

Bioprosthesis

266 57.5 ± 13.2 2.3:1 64

153 55.8 ± 15.4 4:1 51 15 58

9

69 4 5 5 52 21 2.8 18 59

± 9

2 9 4 52 ± 7 21 ± 10 2.8 ± 0.9 18 ± 9

± 15

56 ± 16

± 6 ± 11

± 1.0

30

39

54

49

14

11 1

3

32 5 133 ± 50 81 ± 26

24

4 III ± 42 72 ± 19

p Value

0.53 0.03 0.01

0.08 0.03 0.24 0.08 0.81 0.43 0.54

0.77 0.57 0.17

0.08 0.67 0.00005 0.0001

Legend: NYHA. New York Heart Association. CHF, Congestive heart failure. PA, Pulmonary artery. LVEDP, Left ventricular end-diastolic pressure.

no significant difference was present in hemodynamic status, predominant hemodynamic lesion, and concomitant procedures. Warfarin anticoagulation was begun 2 days after operation for all patients and was continued indefinitely for Bjork-Shiley recipients unless life-threatening hemorrhage occurred, precluding its continued use. Ninetyone percent of hospital survivors were receiving warfarin. Patients with bioprosthetic valves received warfarin for up to 12 weeks after the operation, after which it was usually discontinued. Thirteen percent of bioprosthesis recipients were receiving long-term warfarin therapy. Standard definitions of valve-related complications previously described were employed. 2.3 Any new focal or diffuse neurologic event, permanent or transient, appearing after operation or during the follow-up interval was considered to be a thromboembolus. Patients who did not regain consciousness or who awoke with a neurologic deficit immediately after the operation were excluded. If another source could be conclusively identified as a cause of the neurologic event, then the episode was not considered valve related. Visceral or extremity vessel emboli were included in this determination. Valve thrombosis was identified and confirmed at autopsy or at reoperation, Valve thrombosis and thromboemboli

were combined to represent total thrombotic events. Episodes of anticoagulant-related hemorrhage (ACH) were considered to be valve related if fatal or severe enough to necessitate hospitalization. Minor hemorrhagic episodes, although the potential significance, were not included. Prosthetic valve endocarditis (PVE) was defined as an episode of septicemia in the absence of a source other than the prosthesis, which necessitated prolonged antibiotic therapy or reoperation.' Structural valve failure, observed only in bioprosthetic valves, was ascertained at reoperation or autopsy and defined by the presence of characteristic leaflet calcification or cuspal disruption in the absence of PVE.5 Composite valve-related morbidity was the total of all patients experiencing valve-related complications. Frequently, a patient experienced more than one valverelated complication; however, only the first event was considered in this analysis. Composite valve-related mortality included fatalities arising from valve-related morbidity. When multiple valve-related complications led to death, the precipitating event was determined to be fatal. To facilitate comparision of mechanical and bioprosthetic valves, we used a comprehensive definition of valve failure.s ' Simply, any valve-related morbidity, such as a thromboembolus, ACH, PVE, valve thrombo-

22

The JOurnal of Thoracic and Cardiovascular Surgery

Borkon et al.

Table II. Late mortality Bjork-Shiley (19%) No. pts.

7

I

Bioprosthesis (20%)

%

16 31

No. pts.

I

%

31 19

16

8 5 4 5

IS 20

11

-.M

....1

.J2

45

100

26

100

Cardiac Sudden Cancer Other Valve-related

7

Total

14 6

13

sis, periprosthetic leak, prosthetic valve dysfunction caused by loss of structural integrity, or any other reason that necessitated reoperation or resulted in death, was defined as valve failure. Patient follow-up was achieved by direct contact with patients, their primary physicians, or both during a 3 year closing period ending December 1985. Valverelated complications were assessed with the aid of a comprehensive questionnaire. Supplemental information was gleaned, when possible, from autopsy reports and death certificates. Follow-up information was available in all but 11 patients (eight with a Bjork-Shiley valve and three with a bioprosthesis), resulting in a 97% follow-up. A cumulative total of 1,705 patient-years (pt-yrs) was available for analysis (1,077 pt-yrs, BjorkShiley group, and 628 pt-yrs, bioprosthetic valve group). Mean follow-up for all patients was 4.1 ± 2.7 years (range 0 to 9.4 years). Among current survivors, cumulative patient follow-up was 1,496 pt-yrs, (915 pt-yrs, Bjork-Shiley group, and 545 pt-yrs, Bjork-Shiley valve group; the average follow-up for survivors was 5.1 ± 2.2 pt-yrs. There was no difference in mean follow-up for survivors of Bjork-Shiley and bioprosthetic valve replacement. Patients undergoing reoperation for rereplacement of the aortic prosthesis or for additional cardiac valve replacement were censored from analysis and considered to be withdrawn alive or dead depending upon their status 30 days after reoperation. Kaplan-Meier actuarial analysis and linearized statistical determinations of survival rates and incidence of valve-related complications were performed." Actuarial rates were expressed as percent of patients event free. Linearized data were derived from first patient events, expressed as percent per patient-year (%/pt-yr) and compared by the Z test. 7 Continuous data are represented as mean ± 1 standard deviation; linearized rates and actuarial determinations are expressed as mean ± 1 standard error. Factors predictive of survival and freedom from certain valve-related complications were

initially analyzed individually by Kaplan-Meier actuarial analysis and their significance determined by the Breslow test," Significant factors were then entered into a multivariate stepwise Cox proportionate hazards model to identify independent and additive variables associated with length of survival or freedom from complications." The contribution of each variable entered into the model was assessed by the likelihood ratio test. 10 In addition to those variables listed in Table I, other dependent variables entered into univariate and multivariate analysis for all morbid and fatal events included valve type, race, duration of angina, anginal class, urgency of operation, aortic gradient, roentgenographic aortic valve calcium, aortic valve area, left ventricular systolic pressure, left ventricular systolic and diastolic volume, year of operation, valve size, and warfarin status. Results Survival, Overall hospital mortality for both groups from 1976 to 1981 was 12.9% (54/419). The causes of hospital death were not different between Bjork-Shiley and bioprosthetic valve recipients. In both groups, cardiac-related causes accounted for 59% (32/54) of early deaths. One valve-related death, valve thrombosis on postoperative day 6, occurred in a patient receiving a Bjork-Shiley valve. One patient with a bioprosthetic valve died early of a cerebral thromboembolus. Fatalities resulting from cardiac causes and sudden death account for the majority of late deaths (Table II). Excluding patients dying suddenly, valve-related complications were responsible for 24% (11/45) of late deaths in the Bjork-Shiley group and 15% (4/26) in the bioprosthesis group. If sudden deaths are assumed to be valve related, then 78% (35/45) of late deaths in the Bjork-Shiley group and 26% (9/34) in the bioprosthesis group were due to valve-related complications. ACH accounted for 20% of late deaths among Bjork-Shiley recipients, whereas 12% of late deaths in the bioprosthetic valve group were due to a thromboembolus. The 5 year actuarial survival rate (Fig. 1) was 81% ± 4%, identical for hospital survivors in the two valve groups. If hospital deaths are included, the 5 year actuarial survival rate was 72% ± 3% for Bjork-Shiley and 70%. ± 4% for bioprosthetic valve recipients. The only independent preoperative risk factors predictive of an adverse outcome after operation included congestive heart failure class (p < 0.00(05), endocarditis (p < 0.002), and angina (p < 0.025). Ejection fraction less than 40% (p = 0.02), coronary artery disease necessitating coronary artery bypass (p = 0.04), and atrial fibrillation (p = 0.05), but not valve type, were factors

Volume 94 Number 1 July 1987

Aortic valve replacement 2 3

100....,....--------------------r

...J.. .....1~186) 90 Percent Survival

(119)

1.

80

(~SE)

.I

70

() -

Patients at Risk 81~ 3 Bjork-Shiley (4.2~O.6%/pt.-yr.) Bloprosthesls (4.1

o-

o

~O.8%/pt.-yr.)

I

I

I

I

I

1

2

3

4

5

6

7

Years Postoperative

8

Fig. 1. Actuarial survival depicted for hospital survivors. SE. Standard error. NS. Not significant.

II

100.,.,....-........- - - - - - - - - - - - - - - - - - r

.-, ................... 1(119) 1 1~~~~...

~2

. . . . . . . . (49)

Percent Free From Valve-Related Mortality 95 (~SE)

.I

( ) Patients at Risk -

oo

(75)

.

}N.S.

Bjork-Shiley (1.1 ~0.3%/pt.-yr.) Bloprosthesls (0.8 I

1

I

2

I

3

~0.4%/pt.-yr.) I

4

I

5

6

Years Postoperative

7

8

r -

Fig. 2. Actuarial survival free from valve-related mortality.

independently predictive of a fatal late outcome when hospital deaths were excluded. The actuarial survival rate free from valve-related mortality was 95% ± 2% for Bjork-Shiley and 97% ± 2% for bioprosthetic valve recipients at 5 years (Fig. 2). If sudden deaths are included, 89% ± 2% of Bjork-Shiley and 93% ± 3% of bioprosthetic valve recipients were free from valverelated death at 5 years. A high incidence of valverelated mortality was found in the first year (3.2% ± 1.2%/pt-yr, Bjork-Shiley group, and 1.6% ± 1.1%/ptyr, bioprosthesis group), which diminished to 0.6% ± O,3%/pt-yr thereafter for both groups (p < 0.001). Risk factors for valve-related death including sudden death were atrial fibrillation (p = 0.008) and duration of angina (>24 months, p = 0.011), but not valve type. Thrombotic events. Fourteen patients with Bjork-

Shiley valves experienced a thromboembolic event; one patient incurred two such events. Freedom from thromboembolism at 5 and 7 years was 94% ± 2% and 90% ± 3%. The overall linearized rate of thromboembolism was 1.4% ± O.4%/pt-yr. A slightly but not significantly higher rate of thromboembolism was observed in the first postoperative year (2.2% ± 1%/ pt-yr), decreasing (1.1% ± 0.1%/pt-yr) thereafter. One patient was not receiving warfarin and two patients had poor regulation of anticoagulation at the time of the first thromboembolus. Central nervous system (CNS) events accounted for 80% (12/15) of thromboembolic and peripheral arterial emboli occurred in 20% (3/15). Seventy-five percent of CNS events were permanent, with one death. One of three peripheral emboli proved fatal. The actuarial incidence of fatal thromboembolism was 1% at 5 years (0.1% ± O.1%jpt-yr). One patient

The Journal of Thoracic and Cardiovascular Surgery

24 Borkon et al.

100..,.,.....-------------------r

Percent Free From Thrombotic Event ( ~SE)

90

80

f;;;;k

.I

(68)

}N.S. (38)

85~4

( ) Patients at Risk - Bjork-Shiley (1.6~0.4%/pt.-yr.)

oo

Bloprosthesls (2.7

I

1

I

2

~0.7%/pt.-yr.)

I

I

I

3 4 5 6 Years Postoperative

7

8

r

Fig. 3. Actuarial estimate of freedom from any thrombotic event (including thromboembolus and valve thrombosis).

90 Percent Free From

ACH

p< 0,001

80

70

(~SE)

60

.I

oo

( ) Patients at Risk - Bjork-Shiley (6.2~0.8%/pt.-yr.) Bloprosthesls (0.3 I

I

1

2

I

~O.2%/pt.-yr.) I

I

3 4 5 6 Years Postoperative

7

8

r

Fig. 4. Actuarial estimate of freedom from anticoagulant-related hemorrhage (ACH).

with a Bjork-Shiley valve, despite therapeutic anticoagulation, experienced two episodes of CNS thromboembolism, 7 months apart. One or more thromboembolic episodes occurred in 15 patients with bioprosthetic valves. Two patients experienced more than one thromboembolus. Freedom from thromboembolism at both 5 and 7 years was 85% ± 4%. The overall linear rate of thromboembolism for bioprosthetic valves was 2.7% ± 0.7%, significantly greater than that for Bjork-Shiley valves (p = 0.02). The incidence of thromboembolism was slightly but not significantly greater for the first (3.4% ± 1.7%jpt-yr) than for subsequent years (2.5% ± 0.8%jpt-yr). Thirteen ,CNS events occurred and resulted in nine permanent deficits. Death due to thromboembolism occurred in three patients, all with CNS events. The overall linearized rate of fatal thromboembolism for the bioprosthe-

tics group was 0.5% ± 0.3%jpt-yr or 3% at 5 years. The two patients with more than one thromboembolus both had simultaneous CNS and peripheral emboli associated with PVE, in the absence of warfarin anticoagulation. PVE was demonstrated to be the only independent predictor of thromboembolism for bioprosthetic valves (p = 0.006) In fact, three of nine patients with PVE had a thromboembolus. If bioprosthetic valve recipients with PVE are excluded from analysis of thromboembolism, the overall hazard rate for development of thromboembolism is reduced to 2.1% ± 0.6%jpt-yr. Valve thrombosis was observed in only two patients, both with Bjork-Shiley valves. One patient, dying suddenly on the fifth postoperative day, was found at autopsy to have valve thrombosis. Despite seemingly therapeutic anticoagulation, valve thrombosis developed 13 months after operation in another patient. Urgent

Volume 94 Number 1 July 1987

Aortic valve replacement 2 5

100~~-r--r--------------..,.

<, Percent Free From PVE

(!SE)

1

92!3j,;;) ••••••

.I

( ) Patients at Risk - Bjork-Shiley (O.3!O.2%/pt.-yr.)

o-

o

r

Bloprosthesls (1.6 !O.5%/pt.-yr.) I

1

I

2

I

I

I

345

6

Years Postoperative

7

8

-

Fig. 5. Actuarial estimate of freedom from prosthetic valve endocarditis (PVE). 100 ....----o:':":':':"""""'~_:__---------"""T (119)

Percent Free From Failure (!SE)

90 '.

80 ( ) Patients at Risk ~

0+---+---+---+--+---1--1---+--+---+ 8 34567 o 1 2 Years Postoperative

Fig. 6. Actuarial estimate of freedom from bioprosthetic structural valve failure.

thrombectomy was performed successfully. The overall hazard rate of valve thrombosis was 0.2% ± 0.1%/pt-yr for Bjork-Shiley patients. For comparative analysis, thromboembolism and valve thrombosis were combined to obtain a total thrombotic event rate (Fig. 3). The actuarial estimate of freedom from any thrombotic event was 93% ± 2% for Bjork-Shiley and 85% ± 4% for bioprosthetic valves at 5 years (NS*). The overall hazard rate for this event was 1.6% ± O.4%/pt-yr for Bjork-Shiley and 2.7% ± O.7%/pt-yr for bioprosthetic valves (p = 0.05). The annual mortality hazard was 0.2% ± 0.1%/pt-yr for Bjork-Shiley and 0.5% ± 0.3% for bioprosthetic valve recipients (NS). ACH. Fifty-six patients with Bjork-Shiley valves experienced a total of 68 episodes of ACH. The *NS = No significant difference.

actuarial estimates of freedom from ACH (Fig. 4) were 76% ± 3% and 62% ± 5% at 5 and 7 years, respectively, after operation. Nine late deaths were attributed to ACH. At 5 and 7 years, 96% ± 1% and 95% ± 2% were free from fatal ACH. The hazard for this complication in Bjork-Shiley recipients was greatest within the first postoperative year (10.3% ± 2.3%/pt-yr); thereafter, a relatively constant rate of 5.0% ± 0.8%/pt-yr was observed (p < 0.006). Two patients with bioprosthetic valves had a total of three episodes, without a fatality. Both patients experienced ACH after the second postoperative year. Actuarial freedom from ACH for patients with bioprosthetic valves was 99% ± 1% at 5 years. The linearized rate of first ACH for patients with Bjork-Shiley valves was 6.2% ± 0.8% compared to 0.3% ± 0.2%/pt-yr for bioprosthetic valve recipients (p < 0.001). Seventeen percent (12/71) of the cases of ACH were intracerebral and 48% (34/71) were gastro-

The Journal of Thoracic and Cardiovascular Surgery

2 6 Borkon et al.

100 """=:::::::::;;:::;::;::::::;:==::::;:::==;:::::::::;;::::::::;:::==:;:::::=-'1 I .·f....... .... 1(133) ' " I (73) I (187) Y ' .. 99~ 1

y.....

90

Percent Free From Reoperatlon

""r.~~+ 1

,ro"

(40)

p( O.'lI5

.

(~SE)

80

( ) Patients at Risk Blork-Shlley (0.2~0.1%/pt.-yr.)

~;; -

•• Bloprosthesls (1.7

~0.5%/pt.-yr.)

O+--+--+--i--+--+--+--I--~I----+

o

1

2

34567

Years Postoperative

8

Fig. 7. Actuarial estimate of freedom from reoperation.

20 • Bjork-Shiley Bioprosthesis EEl Fatal ~

Number of Patients

15

10

14

85%

14

36%

9 100% 5

5 0

0 Thrombotic ACH Event

PVE

PPL

Structural TOTAL Failure

Fig. 8. Distribution and mortality rates from various causes of valve failure. ACH, Anticoagulant-related hemorrhage. PVE, Prosthetic valve endocarditis. PPL, Periprosthetic leak.

intestinal. The overall incidence of fatal ACH was 1.0% ± O.3%/pt-yr. Eight of nine deaths from ACH were due to intracerebral hemorrhage. One patient died of delayed tamponade 1 week after operation. Multivariate analysis disclosed only valve type to be predictive of an increased risk of ACH. PVE. PVE occurred in three patients with BjorkShiley valves, all of whom received prolonged antibiotic therapy, with one death. Nine patients with bioprosthetic valves experienced PVE; five required reoperation, with one death, and four received prolonged antibiotic therapy. The actuarial probability of being free from PVE (Fig. 5) at 5 years for Bjork-Shiley valve recipients was 98% ± I% and for bioprosthetic valve recipients, 92% ± 3% (p = 0.039). The overall linearized incidence of PVE was 0.3% ± 0.2%/pt-yr for Bjork-Shiley and

1.6% ± 0.5%/pt-yr for bioprosthetic valves (p = 0.029). PVE was observed only within the first year for Bjork-Shiley recipients (1.4% ± 0.8%/pt-yr). On the other hand, bioprosthesis recipients had a relatively constant annual hazard of PVE (1.6% ± 0.5%/pt-yr). The actuarial estimate of freedom from valve failure because of PVE was 99.6% ± 0.4% for Bjork-Shiley and 96% ± 2% for bioprosthetic valves at 5 years, an overall linearized rate of 0.1% ± 0.1%/pt-yr for BjorkShiley and 0.9% ± O.4%/pt-yr for bioprosthetic valve recipients (p = 0.04). Multivariate analysis revealed an increased risk of PVE associated with the Ionescu-Shiley valve (p = 0.002). Structural failure. Structural failure in the absence of PVE was identified in six patients with bioprosthetic valves. Five patients underwent reoperation without a

Volume 94 Number 1 July 1987

Aortic valve replacement 2 7

100.....-.---......,..,=.-------------~

Percent Free From Valve Failure

90 80

(~SE)

70

.I

() -

o-

o

Patients at Risk Bjork-Shiley (1.3~O.3%/pt.-yr.) Bloprosthesls (2.2 I

1

I

2

I

3

~O.6%/pt.-yr.) I

4

I

5

6

Years Postoperative

7

8

r

Fig. 9. Actuarial estimateof freedom from valve/failure defined in a comprehensive fashion.

fatality. One patient refused reoperation and died. Actuarial freedom from structural bioprosthetic failure (Fig. 6) was 99% ± 1% and 89% ± 5% at 5 and 7 years, respectively. Because the annual hazard of this event occurred at an accelerating rate, calculation of a linear rate may be misleading. Patients less than 36 years old had a higher risk of structural bioprosthetic failure (p < 0.03) than did older patients. In fact, either intrinsic structural failure or PVE developed in 40% (6/16) of patients under the age of 35, compared to 4% (5/127) of patients over the age of 35 (p < 0.001). Multivariate analysis confirmed age examined as a continuous variable (p = 0.014) and Ionescu-Shiley valve (p = 0.006) to be risk factors for bioprosthetic structural failure. One patient with a Bjork-Shiley valve developed a bland periprosthetic leak after aortic valve replacement and underwent successful reoperation. Reoperation. Valve rereplacement was required in 12 patients, two with Bjork-Shiley and 10 with bioprosthetic valves. Perivalvular leak and valve thrombosis had accounted for two reoperations in the Bjork-Shiley group; endocarditis (five patients) and structural failure (five patients) were responsible for 10 reoperations in the bioprosthesis group. The actuarial estimate of freedom from reoperation (Fig. 7) was 99% ± 1% for Bjork-Shiley valves at 5 and 7 years, respectively, compared to 94% ± 3% and 86% ± 5% at 5 and 7 years, respectively, for bioprosthetic valves (p = 0.04). The overall linear incidence of reoperation was 0.2% ± O.1%/pt-yr for Bjork-Shiley and 1.7% ± 0.5%/pt-yr for bioprosthetic valves. The annual hazard for reoperation in bioprosthetic valves increased with the duration of follow-up, reflecting an increased number of patients with intrinsic bioprosthetic failure. Only one patient in

the bioprosthesis group with endocarditis died at reoperation, a 10% reoperative mortality rate. Multivariate analysis showed PVE (p = 0.01), age less than 35 (p = 0.0007), and Ionescu-Shiley valve (p = 0.00005) to be associated with the need for reoperation. Valve failure. Patients who died of valve-related events (valve-related mortality) or who underwent reoperation were considered to have experienced valve failure (Fig. 8). Accordingly, there were 14 patients in each group. ACH accounted for over 64% (9/14) of failures of Bjork-Shiley valves and was uniformly fatal. Reoperation was needed in 71% (10/14) of the valve failures in the bioprosthetic valve group, which were due to either PVE or intrinsic structural deterioration. Structural failure of Bjork-Shiley valves was not observed. Overall, 86% (12/14) of Bjork-Shiley patients with valve failure died compared to 36% (5/14) of patients with bioprosthetic valves (p < 0.01). Actuarial estimates of freedom from valve failure (Fig. 9) at 5 and 7 years for Bjork-Shiley valves were 93 ± 2% and 91% ± 3% and for bioprosthetic valves, 91% ± 3% and 79% ± 7%, respectively. The annual hazard of valve failure for Bjork-Shiley valves was greater within the first year 3.6% ± 1.3% than it was thereafter (0.7% ± O.3%/pt-yr) (p < 0.001). The annual hazard rate for bioprosthetic valve failure in the first year was 1.6% ± 1.1 %/pt-yr. Within the first 4 years after operation the hazard rate for bioprosthetic valves was 1.3% ± 0.5%/ pt-yr, compared to 6.6% ± 2.5%/pt-yr for the fifth through eighth postoperative year (p < 0.001). Composite valve-related morbidity. One or more valve-related complications were observed in 70 patients with Bjork-Shiley and 27 patients with bioprosthetic valves (Fig. 10). Leading causes of valve-related morbid-

The Journal of Thoracic and Cardiovascular

2 8 Borkon et al.

Surgery

80-r----------------------• Bjork-Shiley 1:3 Bloprosthesls IB Fatal

Number 30 of Patients

20

10

Thrombotic

ACH

PVE

Event

PPL

Structural

Re-

Velve

Failure

operation

FaMure

TOTAL

Fig. 10. Distribution of mortality rates for various causes of valve-realted morbidity. ACH, Anticoagulant-related hemorrhage. PVE, Prosthetic valve endocarditis. PPL, Periprosthetic leak.

Table ill. Summary of rates of valve-related morbidity Bioprosthesis

Bjork-Shiley No. Thrombotic event

ACH

PVE PPL

Structural failure Reoperation Valve failure Total

16 56

3 1

o 2 14 70

I

Rate (%/pt-yr)

No.

± 0.4 ± 0.8 ± 0.2 ± 0.1

15 2 9

0.2 ± 0.1 J.3 ± 0.3 7.9 ± 0.9

10

1.6 6.2 0.3 0.1

I

o 6

14 27

Rate (%/pt-yr)

p Value

2.7 ± 0.7 0.3 ± 0.2 1.6 ± 0.5

0.05 0.001 0.03

± 0.4 ± 0.5 ± 0.6 ± 0.9

0.001 0.001 0.156 0.03

1.0 1.7 2.2 4.9

Legend: ACH, Anticoagulant-related hemorrhage. PYE, Prosthetic valve endocarditis. PPL, Periprosthetic leak.

ity were thrombotic events and ACH for patients with Bjork-Shiley valves. Thrombotic events, PVE, and structural failure were the most common complications observed in bioprosthetic valve recipients. Summarized in Table III are the various causes of valve-related morbidity. Because of a number of patients who experienced more than one valve-related complication, the sum of hazard rates for all valve-related complications appears greater than the composite total. Actuarial estimates of freedom from valve-related morbidity (Fig. 11) were 70% ± 3% and 56% ± 5% for Bjork-Shiley recipients and 81% ± 4% and 74% ± 5% for bioprosthetic valve recipients at 5 and 7 years respectively, (p < 0.05). The overall rate ofvalve-related morbidity expressed in linear terms was 7.9% ± 0.9%/ pt-yr for Bjork-Shiley and 4.9% ± 0.9%/pt-yr for bio-

prosthetic valve replacement (p = 0.027). The observed rate was highest in the first postoperative year (p < 0.00(4) for Bjork-Shiley valves (14.4% ± 2.2%/ pt-yr) compared to thereafter (4.2% ± l.l%jpt-yr). The annual rate was constant for bioprosthetic valves.

Discussion The Bjork-Shiley valve is exceeded only by the Starr-Edwards prosthesis in duration of use and number of patient implants. Recent analysis of the standardorifice Bjork-Shiley valve found it to be similar to the Starr-Edwards 1260 model with respect to valve-related morbidity and mortality.' Beginning in 1976, bioprosthetic heart valves were introduced and used with increasing frequency at our institution. Thus, during a subsequent 5 year period from 1976 to 1981, two nearly

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Aortic valve replacement 2 9

Number 1 July 1987

100~----------------""T

90 Percent Free From 80 Valve-Related Complication 70 (!SE)

60

.I

( ) Patients at Risk - Bjork-Shiley (7.9~O.9%/pt.-yr.)

o-

o

Bloprosthesls (4.9 I

1

I

2

I

~O.9%/pt.-yr.) I

I

345

6

Years Postoperative

7

8

t

Fig. 11. Actuarial estimate of freedom from any valve-related complication. identical populations of patients, one receiving mechanical and the other bioprosthetic heart valves, were available for long-term retrospective analysis of valverelated complications. Both groups had similar preoperative clinical characteristics except that a greater number of Bjork-Shiley recipients had New York Heart Association Functional Class III and IV congestive failure and a history of angina. Preoperative hemodynamic evaluation, however, disclosed nearly identical ejection fractions, cardiac indices, and left ventricular end-diastolic pressures for both groups. Although the percentageof concomitant coronary artery bypass operationsperformed was slightly higher in the Bjork-Shiley than in the bioprosthetic valve group, multivariate analysis confirmed that differing preoperative variables between the two groups were not related to development of subsequent valve-related events. Survival is a relatively insensitive measure of overall valve performance and is principally influenced by patient-related factors. No difference in survival was discerned between bioprosthetic and Bjork-Shiley valve recipients, similar to other published figures. I 1-21 As in most reported series, the majority of late deaths were cardiac related." In the absence of a postmortem examination, patients who died suddenly were placed in thegroup of cardiac-related deaths. We believe that the majority of these patients died of an arrhythmia, but it is possible that some patients may actually have died of a valve-related cause." Computation of valve-related mortalityincorporating sudden death did not yield different results. In fact, multivariate analysis demonstrated only atrial fibrillation and duration of angina, but not valve type, to be independent risk factors for this group. The incidence of thromboemboli was found to be significantly greater for bioprosthetic than Bjork-Shiley

valves, an observation conflicting with previous reports.II-21.23-26 If patients with thromboembolism related to PVE were eliminated from the bioprosthesis group, the difference between groups did not achieve statistical significance. On the other hand, a relatively low incidence of thromboembolism was recognized in the Bjork-Shiley group.":" The importance of time frame analysis is emphasized, because before 1976 the thromboembolism rate was 3.1% ± O.5%/pt-yr for Bjork-Shiley patients, a rate significantly greater than that observed in the present study (p < 0.02).2 The lower incidence of thromboembolism in Bjork-Shiley patients may have been offset by a relatively high rate of ACH. Valve thrombosis was observed in only two patients with Bjork-Shiley valves. Although a rare complication, its presentation is abrupt and frequently associated with a high mortality rate. This valve-related complication has been widely recognized with tilting disc mechanical valves, often occurring despite adequate anticoagulation.II-15.27 An ever-present risk and unavoidable complication of warfarin anticoagulation is ACH. Although diminished after the first postoperative year, the hazard rate of ACH remained substantial, similar to findings of other investigations. 11-15 ACH accounted for 80% of late valve-related morbidity and 75% of valve-related deaths for Bjork-Shiley recipients. Only 10% of patients with bioprosthesis were receiving warfarin; thus a low incidence of ACH was found for the bioprosthetic valve group. The high incidence of ACH detracts from the safety of all mechanical prostheses.': 11-15.20.23.24.26.28-31 A slightly higher incidence of PVE was noted for bioprosthetic valve than for Bjork-Shiley valve recipients. An independent risk factor for PVE was the

The Journal of Thoracic and Cardiovascular Surgery

3 0 Borkon et al.

presence of an Ionescu-Shiley valve. Other authors have not found a difference in the rate of PVE for mechanical and bioprosthetic valves." 32 However, bioprosthetic valves may be more predisposed to develop PVE than mechanical valves when implanted in the setting of native valve endocarditis." In the present study the incidence of preoperative native valve endocarditis was slightly greater for bioprosthetic and Bjork-Shiley valve recipients. PVE was recognized in Bjork-Shiley patients only within the first postoperative year. It is possible that subsequent events were not identified because of the technique of retrospective follow-up analysis. Similar to other reports, PVE treated medically or by reoperation was accompanied by a high mortality rate irrespective of valve type.2, 3,11·19 Structural bioprosthetic valve failure has been observed with increasing frequency beyond the fifth postoperative yearY.,·19,20,21,26,29 Unlike mechanical valve failure caused by valve thrombosis or strut fracture, which may occur suddenly and is often fatal, structural failure of bioprosthetic valves was associated with a gradual onset of symptoms permitting safe reoperation. In the absence of severe congestive heart failure or PVE, reoperation for bioprosthetic failure may be performed with an operative mortality identical to that of the original operation.v" The ability to recognize structural bioprosthetic failure by noninvasive imaging may enhance reoperative survival.37 Of note was a higher rate of structural failure (p < 0.03) observed in patients less than 36 years old16 and with Ionescu-Shiley valves.v 39 The poor results found with the Ionescu-Shiley valve may have adversely biased the outcome of the bioprosthesis group as a whole. Determination of the incidence of valve-related morbidity and mortality and valve failure based upon a comprehensive definition facilitates comparison of different valve types. In the present study, the incidence of valve failure was nearly identical for Bjork-Shiley and bioprosthetic valves at 5 years. With increasing duration of follow-up, the number of patients with bioprosthetic structural deterioration increased, which resulted in a higher although statistically not significant incidence of valve failure among bioprosthetic compared to BjorkShiley valve recipients. The mortality resulting from valve failure was much greater for patients with BjorkShiley than bioprosthetic valves. Total valve-related morbidity was found to be substantially less for bioprosthetic than Bjork-Shiley valve recipients for up to 7 years after operation. Other studies comparing bioprosthetic and mechanical valve substitutes have revealed similar conclusions.20, 26, 28·32. 34 Finally, although statistically not significant, it appeared that

valve-related mortality was also reduced for bioprosthetic valves. Thus, for up to 7 years after operation, the bioprosthetic valve appears to offer a greater margin of safety than the Bjork-Shiley substitute. Continued analysis will be required to determine which valve will ultimately provide the greatest long-term patient safety. REFERENCES 1. Mitchell RS, Miller DC, Stinson EB, et al. Significant patient-related determinants of prosthetic valve performance. J THORAC CARDIOVASC SURG 1986;91:807. 2. Borkon AM, Soule LM, Baughman KL, et al. Ten year analysis of the Bjork-Shiley standard aortic valve. Ann Thorac Surg (in press). 3. Miller DC, Oyer PE, Mitchell RS, et al. Performance characteristics of the Starr-Edwards Model 1260 aortic valve prosthesis beyond ten years. J THORAC CARDIOVASC SURG 1984;88:193. 4. Baumgartner WA, Miller DC, Reitz BA, et al. Surgical treatment of prosthetic valve endocarditis. Ann Thorac Surg 1983;35:87. 5. Spray TL, Roberts We. Structural changes in porcine xenografts used as substitute cardiac valves. Am J Cardiol 1977;40:319. 6. Lefrak EA, Starr A, eds. Cardiac valve prostheses. New York: Appleton-Century-Crofts, 1979:38. 7. Snedecor GW, Cochran WG. Statistical methods, 7th ed. Ames, Iowa: Iowa State University Press, 1980:41. 8. Breslow N. A generalized Kruskal-Wallis test for comparing K samples subject. to unequal patterns of censorship. Biometrika 1970;57:579. 9. Cox DR. Regression models and life tables. J R Stat Soc (B) 1972;26:103. 10. BMDP Statistical Software. Dixon WJ, ed. Berkeley, California: University of California Press, 1985. II. Karp RB, Cyrus RJ, Blackstone EH, Kirklin JW, Kouchoukos NT, Pacifico AD. The Bjork-Shiley valve. J THORAC CARDIOVASC SURG 1981;81:602. 12. Cohn LH, Allred EN, DiSesa VJ, Sawtelle K, Shemin RJ, Collins JJ Jr. Early and late risk of aortic valve replacement. J THORAC CARDIOVASC SURG 1984;88:695. 13. Bjork va, Henze A. Ten years' experience with the Bjork-Shiley tilting disc valve. J THORAC CARDIOVASC SURG 1979;78:331. 14. Daenen W, Nevelsteen A, van Cauwelaert P, de Maesschalk E, Willems J, Stalpaert G. Nine years' experience with the Bjork-Shiley prosthetic valve: early and late results of 932. valve replacements. Ann Thorac Surg 1983;35:651. 15. Sethia B, Turner MA, Lewis S, Rodger RA, Bain WH, Kouchoukos NT. Fourteen years' experience with the Bjork-Shiley tilting disc prosthesis. J THORAC CARDI0VASC SURG 1986;91:350. 16. Magilligan DJ, Lewis JW, Tilley B, Peterson E. The porcine bioprosthetic valve: twelve years later. J THoRAe CARDIOVASC SURG 1985;89:499.

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17. Cohn LH, Mudge GH, Pratter F, Collins JJ Jr. Five to eight-year follow-up of patients undergoing porcine heartvalve replacement. N Engl J Med 1981;304:258. 18. Hartz RS, Fisher EB, Finkelmeier B, et al. An eight-year experience with porcine bioprosthetic cardiac valves. J THORAC CARDIOVASC SURG 1986;91 :910. 19. Oyer PE, Miller DC, Stinson EB, Reitz BA, MorenoCabral RJ, Shumway NE. Clinical durability of the Hancock porcine bioprosthetic valve. J THORAC CARDJOVASC SURG 1980;80:824. 20. Hammond GL, Geha AS, Kopf GS, Hashim SW. Biological versus mechanical valves: analysis of 1,116 valves inserted in 1,012 adult patients with a 4,818 patient-year follow-up. J THORAC CARDIOVASC SURG 1987;93:182. 21. Janusz MT, Jamieson WRE, Allen P, et al: Experience with the Carpentier-Edwards porcine valve prosthesis in 700 patients. Ann Thorac Surg 1982;34:625. 22. Tepley JF, Grunkemeier GL, Sutherland HD, Lambert LE, Johnson .yA, Starr A. The ultimate prognosis after valve replacement: an assessment of twenty years. Ann Thorac Surg 1981;32:111. 23. Gersh BJ, Fisher LD, Schaff HV, et al. Issues concerning the clinical evaluation of new prosthetic valves. J THORAC CARDIOVASC SURG 1986;91 :460. 24. Martinell J, Fraile J, Artiz V, Moreno J, Rabago G. Long-term comparative analysis of the Bjork-Shiley and Hancock valves implanted in 1975. J THORAC CARDlOVASC SURG 1985;90:741. 25. Jamieson WRE, Janusz MT, Miyagishima RT, et al. Embolic complications of porcine heterograft cardiac valves. J THORAC CARDIOVASC SURG 1981;81:626. 26. Joyce LD, Nelson RM. Comparison of porcine valve xenografts with mechanical prostheses. J THORAC CARD10VASC SURG 1984;88:102. 27. Wright JO, Hiratzka LF, Brandt B, Doty DB. Thrombosis of the Bjork-Shiley prosthesis. J THORAC CARDIOVASC SURG 1982;84:138. 28. Douglas PS, Hirshfeld JW Jr, Edie RN, Harken AH, Stephenson LW, Edmunds LH Jr. Clinical comparison of St. Jude and porcine aortic valve prostheses. Circulation 1985;72(Pt 2):II 135. 29. Mitchell RS, Miller DC, Stinson EB, et al. Perspectives on the porcine xenograft valve. Cardiol Clin 1985;3:371. 30. Starr A, Jamieson WRE, Miller DC, et al. A triinstitutional comparison of tissue and mechanical valves using a patient-oriented definition of treatment failure. Ann Thorac Surg (in press). 31. Perier P, Bessou JP, Swanson JS, et al. Comparative evaluation of aortic valve replacement with Starr, Bjork, and porcine valve prostheses. Circulation 72 1985;(Pt 2):11140. 32. Rutledge R, Kim BJ, Applebaum E. Actuarial analysis of the risk of prosthetic valve endocarditis in 1,598 patients with mechanical and bioprosthetic valves. Arch Surg 1985;120:469. 33. Sweeney MS, Reul GJ Jr, Cooley DA, et al. Comparison

34.

35.

36.

37.

38.

39.

31

of bioprosthetic and mechanical valve replacement for active endocarditis. J THORAC CARDIOVASC SURG 1985; 90:676. Bortolotti U, Milano A, Mazzucco A, et al. Results of reoperation for primary tissue failure of porcine bioprosthesis. J THORAC CARDIOVASC SURG 1985;90:564. Wideman FE, Blackstone EH, Kirklin JW, Karp RB, Kouchoukos NT, Pacifico AD. Hospital mortality of re-replacement of the aortic valve. J THORAC CARDIOVASC SURG 1981;82:692. Husebye DG, Pluth JR, Piehler JM, et al. Reoperation on prosthetic heart valves. J THORAC CARDIOVASC SURG 1983;86:543. Grenadier E, Sahn DJ, Roche AH, et al. Detection of deterioration or infection of homograft and porcine xenograft bioprosthetic valves in mitral and aortic positions by two-dimensional echocardiographic examination. J Am Coli Cardiol 1983;2:452. Nistal F, Garcia-Satue E, Artifiano E, Duran CMG, Gallo I. Comparative study of primary tissue valve failure between Ionescu-Shiley pericardial and Hancock porcine valves in the aortic position. Am J Cardiol 1986;57:161. Reul GJ Jr, Cooley DA, Duncan JM, et al. Valve failure with the Ionescu-Shiley bovine pericardial bioprosthesis: analysis of 2680 patients. J Vase Surg 1985;2:192.

Discussion DR. MICHAEL JANUSZ Vancouver, B. C. Canada

I wish to commend the authors on their methodology of valve assessment and on their achievement of a 97% complete follow-up, which is vital to this type of study. I wish to ask the authors what is meant by a 3 year closing period for data acquisition. I believe that the most reliable data will be achieved by an ongoing annual follow-up on all patients or, failing this, by simultaneous follow-up of all patients performed within a short period. Could you please comment on that? DR. BORKON Thank you for your kind remarks. The 3 year closing period was a logistic requirement to facilitate complete contact with the patients. We are now establishing a prospective analysis of all patients undergoing cardiac valve operations, yet for this study the analysis was obviously done in a retrospective fashion. In part, the follow-up success was due to the long interval of intensive investigation. DR. JANUSZ Another significant problem in most clinical valve studies, and one that is beyond the control of most investigators, is lack of autopsy data. In this study there was a relatively larger number of sudden deaths in the mechanical prosthesis group, which may have been due to sudden valve failure. This is a problem with all studies; and I expect that the authors found some difficulty in that, as well. The authors have noted the advantages of comparing two groups from the same institu-

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3 2 Borkon et aJ.

tion; however, there is also a significant drawback to that, in that the patients from each group were selected by the attending physicians. Also, I wish to ask the authors why these patients are nonconsecutive, and what effect this might have had on the study. DR. BORKON Let me comment on the first portion of your discussion and then answer the question. Autopsy information is often hard to glean because of reluctance of the families. Admittedly, within both groups there may be valve-related deaths that remain undetected and could certainly skew the observations. Valve selection was determined by surgeons' preference. The study was conducted during a time when we were also beginning to use the St. Jude Medical valve, which accounts for the nonconsecutive nature of the patients. There was somewhat of a bias initially in the experience toward younger patients receiving the bioprosthesis, which was offset in the latter portion of the study period by elderly patients receiving the valve. Nevertheless, the age groups were not significantly different. There was also a tendency, because of belief that the Bjork-Shiley valve was more hemodynamically efficient than a bioprosthesis, to insert the Bjork-Shiley valve within smaller aortic roots. However, when multivariate analysis were employed, valve type had no bearing on valve-related events. DR. JANUSZ How many patients in this time period received the St. Jude Medical valve, in round numbers? DR. BORKON Our use of the St. Jude Medical valve began in 1979, which was the last 2 years of the present study. During this time, I think fewer than 50 were implanted. DR. JANUSZ The number of patients in this series is fairly small; hence differences between the two groups may appear important but yet fail to achieve statistical significance. It is similarly difficult to be certain as to how precise we should interpret these figures to be, particularly in comparison to figures from larger series. The incidence of thromboembolic events in the Bjork-Shiley group is unusually low, and the incidence of ACH in this group is quite high. An inverse relationship between ACH and thromboembolism has previously been noted in other mechanical valve series. I think that we are perhaps seeing here both the benefit and the cost of aggressive anticoagulation. The incidence of thromboembolic events in the bioprosthesis group is unusually high and differs substantially from other series and from our own experience with Carpentier-Edwards and Hancock prostheses, in which we found the incidence of major thromboembolic events for aortic valves to be from 0.5% to 1.1%/pt yr. When the three thromboembolic episodes in this series that occurred as a result of infective endocarditis are excluded, there was no statistically significant difference between the two groups with respect to thromboembolism.

Surgery

Patient factors are very important in the risks of thromboembolism after valve replacement. This fact, plus continued improvements in mechanical prostheses, make it increasingly difficult to show a statistically significant difference in thromboembolic rates between mechanical and tissue valve prostheses. An increased incidence of PVE in the bioprosthesis group was noted here. This has also been suggested by other recent studies, although most reports indicate that the rates are the same for those two. However, I think this may be a real phenomenon. It is of some concern to us and a number of other investigators, and it is continuing to be evaluated. The risks of valve failure, of tissue and mechanical prostheses, are well illustrated here. Tissue failure is a major problem, particularly in younger patients, but is usually manageable. Mechanical prosthesis failure is less frequent but more often life-threatening. At the University of British Columbia, we presently implant a tissue valve in 90% of our valve recipients, on the basis of our experience with and our ongoing follow-up of 2,700 tissue valve prostheses. DR. RICHARD M. PETERS San Diego. Calif.

Before the final publication of this paper, might it be advisable for you to redo a set of statistics that would include the sudden deaths as valve related? You could also assume that they are not valve related. Your statistical analysis should present both possibilities. DR. BORKON I recognize this fact is a limitation. Unfortunately, many of these patients with sudden death may have experienced an arrhythmia, which certainly clouds the issues. But that is an important comment. DR. JOHN C. CALLAGHAN Edmonton, Alberta. Canada

We are engaged in a trans-Canada study on another valve that has only recently been released in the United States-the Omniscience valve. We have 413 patients at risk, with four centers reporting. Our rates are similar to 'your results with mechanical valves; we have a thrombosis rate of O.5%/pt-yr and a thromboembolic rate of 1.5%/pt-yr, which have worried us in studying these patients. How carefully did you analyze the patients in terms of their thromboembolic events? We have found that to be extremely difficult to analyze. Did you have neurologists examine them? Did you get your information by telephone? How did you document the event? This is one of the patients that we are addressing, and we are finding it extremely difficult to get accurate information. DR. BORKON I would agree with that observation. We found a relatively higher proportion of permanent events than have other investigators, who have recognized that transient and permanent events probably occur equally. I think that is a reflectionof our insensitivity to detect transient events. We had no difficulty whatsoever in identifying events that were subsequently permanent, so we may have underestimated transient events for both groups.

Volume 94 Number 1 July 1987

DR. CALLAGHAN This has been our impression. Could I ask one more question? I noticed your 6%/pt-yr incidence of serious bleeding episodes. In our trans-Canada series, we have a 1.1 %/pt-yr rate. I was wondering how careful your supervision or the physician's supervision of the warfarin doses has been. I have taken a particular interest in having the patient contribute to the responsibility of his prothrombin times. In your analysis, were you able to find out if it was a casual relationship between a general practitioner, or a clinic, or how did you determine if indeed they were under regular, repetitive control of the prothrombin times and their dosage control?

Aortic valve replacement 3 3

DR. BaRKaN We did not specifically assess that point, which has obvious importance. Our figure of 6% per year is somewhat biased, in that a great deal of anticoagulant-related complications occurred within the first year after operation. If that is excluded, our annual incidence was more in the realm of 4%/pt-yr, which is in line with many other reports in the United States. Certainly, Canada and some of the European reports have reported better anticoagulant results than ours, which I cannot explain. Unfortunately, as surgeons we have little control over the ability to maintain satisfactory and therapeutic anticoagulation.

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