Ten-year experience with the St. Jude Medical valve for primary valve replacement

J

THORAC CARDIOVASC SURG

1990;100:44-55

Ten-year experience with the 81. Jude Medical valve for primary valve replacement The St. Jude Medical valve is a bileaftet prosthesis with excellent hemodynamic characteristics, but the long-tenn surgical experience with this valve, its durability, and its biocompatibility are unknown. During a IO-year period from March 1978 to 1988, 690 prostheses (290 aortic, 252 mitral, and 74 double aortic-mitral) were inserted as the initial valve replacement substitute in 616 patients (mean age 63 years). Coronary atherosclerosis was present in 58 %. Follow-up totaled 2031 patient-years (mean 3.3 years) and was 95% complete (32 lost), Early (3O-day) mortality rates were 5.2%, 11.9%, and 8.1 % after aortic, mitral, and double valve replacement; 5- and 9-year actuarial survival rates were 71 % ± 3% and 51 % ± 8%, 59% ± 4% and 41 % ± 6%, and 69% ± 6% and 47% ± 15%, respectively. Deaths were associated with extensive coronary atherosclerosis (p < 0.001). older age (p < 0.001~ advanced preoperative New York Heart Association functional class (p < O.O~ and malignant ventricular arrhythmias (p < 0.05). No structural failures have been observed. Embolism (40 events) occurred at a rate of 2.0% jpt-yr (2.3% aortic, 1.6% mitral, 2.0% double). There were six cases of valve thrombosis (0.3% jpt-yr; one fatal). Hemorrhage was the most frequent complication (2.6 % jpt-yr); 13 (25 % ) of 52 events were fatal, accounting for 62 % of all valve-related deaths. After the target prothrombin time ratio was lowered, the rate of hemorrhage decreased by 44 % (2.7% to 1.5 % jpt-yr). while the combined rate of embolism and valve thrombosis increased slightly (2.2 % to 2.5% jpt-yr, a 14% change). In summary, the St. Jude Medical valve remains a durable valve substitute. Survival was strongly related to the presence of associated coronary atherosclerosis. The most common complication has been hemorrhage; a less intensive warfarin regimen may reduce hemorrhagic risk while maintaining thromboembolic protection.

Lawrence S. C. Czer, MD, Aurelio Chaux, MD, Jack M. Matloff, MD, Michele A. DeRobertis, RN, Sharon A. Nessim, DrPH,* Debra Scarlata, MS,* Steven S. Khan, MD, Robert M. Kass, MD, Tsung Po Tsai, MD, Carlos Blanche, MD, and Richard J. Gray, MD, Los Angeles. Calif.

h e St. Jude Medical valve is a bileaflet low-profile mechanical prosthesis with excellent hemodynamic performance characteristics.L'" In early clinical studies, the reported rates of thromboembolism and other complications have been IOW. ID- 15 These features have prompted surgeons to use the prosthesis more frequent-

From the Division of Cardiology and the Department of Thoracic and Cardiovascular Surgery, Cedars-Sinai Medical Center, Los Angeles, Calif. Read at the Fifteenth Annual Meeting of The Western Thoracic Surgical Association, Monterey, Calif., June 21-25, 1989. Address for reprints: Lawrence S. C. Czer, MD, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Room 6215, Los Angeles, CA 90048. ·Consultant biostatisticians.

12/6/19317

44

ly when valve replacement is required, and it is now one of the most widely used cardiac valve substitutes. A clinical trial of the St. Jude Medical valve was initiated at our institution in March 1978. High-risk patients, such as the elderly and those with left ventricular dysfunction, ischemic heart disease, or prior valve replacement, were included. A cumulative lo-year experience with the St. Jude Medical valve is reported. Because we wished to examine the consequences of St. Jude Medical valve implantation when the prosthesis was used as the initial valve substitute, patients with prior valve replacement were excluded from this study. Recent recognition of the potential for excessive anticoagulation of prosthetic valve recipients l 6-19 led us to examine the rates of hemorrhage, embolism, and valve thrombosis before and after a change in anticoagulation policy.

Volume 100

St. Jude Medical valve at 10 years 45

Number 1 July 1990

Table I. Preoperative patient characteristics Age (yr) Mean ± SD Range Sex Male Female NYHA class

I-II III IV Cardiac rhythm Normal sinus A Fib VT. sudden death Paced. other History of thromboembolism No Yes Left atrial enlargement None Mild Moderate Severe Left atrial thrombus Absent Present Mitral valve lesion Regurgitation Stenosis Mixed Aortic valve lesion Regurgitation Stenosis Mixed Other Presence of CAD No Yes Extent of CAD Single. double vessel Triple vessel. left main LV ejection fraction (%) Mean ± SD Range LVend-diastolic volume (ml) Mean ± SD Range Stroke volume (ml/m 2) Mean ± SD Range "YHA.

"e" York

63 ± 15 2 - 85 278 (45%) 338 (55%) 37 (6%) 310 (50%) 269 (44%) 394 (64%) 166 (27%) 26 (4'Jr) 30 (5%) 569 (920/<) 47 (8'fr) 245 116 188 59

(40%) (19%) (31%) (10%)

Table II. Operative characteristics Aortic prosthetic size (mm) 19-21 23-25 27-29' 31-33 Mitral prosthetic size (mm) 19-21 23-25 27-29 31-33 Coronary artery bypass grafts Patients Grafts/patient (range) Intraaortic balloon No Yes Additional procedures Tricuspid valve repair Mitral valve repair Aneurysmectomy Aortic graft Ventricular septal defect repair "lncludcs one patient with a 26

I11Ill

161 (45'lr) 168 (46%) 34 (9%) I (0.3%) I (0.3%)

20 (6%) 188 (58%) 117 (36%) 297 (48%) 2.5 ± 1.1 (1-6) 560 (91%) 56 (90/<) 25 (4%) II (2%) 14 (2%) 9 (2%) 3 (0.5%)

aortic valve.

597 (97%) 19 (3%) 173 (53%) 86 (26%) 67 (21%) 62 (17%) 207 (57%) 94 (26%) 1(0.3%) 259 (42%) 357 (58%) 147 (41%) 210 (59%) 59 ± 20 13 - 97 158 ± 79 50- 461 31 ± 9 7 - 79

Hearl Association: A Fib. atriallibrillation: VT. ventricular left ventricular: SD. standard

t..ichvcardia: CAD, coronary artery disease: LV,

deviation.

Methods Patients. From March 1978 to 1988,616 patients underwent single aortic (n = 290), single mitral (n = 252), or double aortic-mitral (n = 74) valve replacement with 690 St. Jude Medical prostheses. The operation was the initial valve replacement

procedure for all patients; those with prior valve replacement (n = 65) were excluded from the study. Also excluded were patients (n = 17) with triple valve replacement, double valve replacement in which the second valve was not a St. Jude Medical prosthesis, and tricuspid valve replacement alone or in combination with another valve replacement, because of small numbers in these different groups. All patients over 40 years of age had preoperative coronary angiography. Preoperative characteristics of the study population are shown in Table I. The mean age was 63 years (range 2 to 85). The preoperative New York Heart Association (NYHA) class was III or IV in 94%. Concomitant coronary atherosclerosis was present in 58%; of these, 59% had triple vessel or left main disease. The mean left ventricular ejection fraction was 59%; it was less than 55% in 39% of patients. Surgical technique. Cardiopulmonary bypass was performed with a bubble or membrane oxygenator. In all patients, myocardial preservation consisted of systemic hypothermia (20° to 25° C), topical cooling with electrolyte solution (Normosol), and intermittent multidose potassium cardioplegia (St. Thomas' Hospital, Plegisol [Abbott Laboratories, N. Chicago, Ill.], or modified blood solution) which was infused into the aortic root or coronary ostia at 4 ° C. When coronary artery bypass grafting was performed with saphenous vein, the distal anastomoses were performed first, followed by valve excision and replacement, and finally the proximal anastomoses. Technical aspects of St. Jude Medical valve implantation have been described previously.P Of the 364 aortic or double aortic-mitral recipients, 91% had prosthetic sizes from 19 to 25 mm. Of the 326 mitral or double aortic-mitral recipients, 94% had prosthetic sizes from 27 to 33 mm. Concomitant coronary artery bypass grafting with saphenous vein or the internal thoracic artery was performed in 297 patients (48%); an additional 18 (3%) had undergone prior

The Journal of

4 6 Czer et al.

Thoracic and Cardiovascular Surgery

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7

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39 41 20

29 25 14

25 13 5

10

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79 113 35

58 73 28

6 3 2

Fig. 1. Actuarial survival after St. Jude Medical valve replacement, stratified by valve position. Survival was significantly lower after mitral valve replacement than after aortic or double valve replacement (p < 0.01). All deaths (early and late) were included in the analysis. The box inset depicts the percent of patients surviving at 30 days,S years, and 9 years. Numbers below figure indicate patients at risk during follow-up.

Table III. Mortality and causes of death by valve position Mortality Time period Early (~30

days)

Late (>30 days)

Causes of death Cardiac

Valve position

Rate (%)*

Deaths

Cardiac valvular

nonvalvular

Noncardiac

Unknown

Aortic (n = 290) Mitral (n = 252) Double (n = 74) All (n = 616)

5.2 11.9 8.1 8.3

15 30 6 51

0 3 0 3

9 22 4 35

6 5 2 13

0 0

0

Aortic (n = 275) Mitral (n = 222) Double (n = 68) All (n = 565)

5.6 8.3 5.2 6.6

53 62 15 130

8 5 5 18

21 41 7 69

23 16 3 42

I 0 0 I

a

'Early mortality rate = dcathsy». late mortality rate = deaths per 100 patient-years of follow-up after 30 days.

bypass operations without need for graft revision. Other concomitant procedures are listed in Table II. Anticoagulant therapy. Warfarin anticoagulation was instituted within 72 hours after the operation. Before Oct. I, 1987, the target prothrombin time was 1.5 to 2.5 times the control value; after Oct. I, 1987, the target prothrombin time was lowered to 1.5 to 2.0 times the control value." In patients at increased risk for thromboembolism, such as those with sus"tained atrial fibrillation, a finding of left atrial thrombus at

operation, a prior history of thromboembolism, or a very enlarged left atrium, dipyridamole (300 to 400 mg daily) was added to warfarin." Patients with recurrent warfarin-related bleeding or contraindications to anticoagulant therapy were placed on an anti platelet regimen of aspirin and dipyridamole. No form of anticoagulant or antiplatelet therapy was maintained in a small number of valve recipients because of severe bleeding complications or patient noncompliance. Postoperative follow-up. Hospital survivors have been con-

Volume 100

St. Jude Medical valve at 10 years 47

Number 1 July 1990

100

None Single or Double Vessel CAD Triple Vessel or Left Main CAD

90 80

p
70

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60

> 50 .S;

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20 10 0 0

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7

8

9

10

Years 259

198

167

135

101

73

51

38

24

8

147

116

99

82

59

42

28

19

11

1

109

87

67

44

21

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210

139

Fig. 2. Actuarial survival after St. Jude Medical valve replacement, stratified by extent of associated coronary artery disease (CAD). A marked detrimental impact of coronary artherosclerosis is apparent. tacted yearly by means of a mailed questionnaire or telephone interview. Most patients have also been examined in our offices. Follow-up duration has been up to 10.5 years and averaged 3.3 years. Patient-years of follow-up were 967 for aortic, 771 for mitral, and 293 for double valve replacement; total follow-up was 2031 patient-years. Thirty-two patients (5.2%) were lost to follow-up. Valve-related complications were defined as structural failure, valve thrombosis, embolism, warfarin-related bleeding necessitating hospitalization, hemolysis, infectious endocarditis, paravalvular leak, and erosion of the atrioventricular groove. Criteria for embolization were cerebral ischemic events with permanent neurologic sequelae; transient unexplained episodes of hemiparesis, visual or speech impairment, dizziness, or loss of memory; or sudden occurrences of abdominal or peripheral pain and ischemia (peripheral embolization). Deaths were classified as early (within 30 days of operation) or late (greater than 30 days postoperatively). On the basis of clinical and autopsy findings, causes of death were classified as cardiac valvular, cardiac nonvalvular, or noncardiac. Cardiac valvular deaths could be attributable to warfarin-related hemorrhage, embolism, stroke, valve thrombosis, valve erosion, bacterial endocarditis, prosthetic dysfunction, or para valvular leak. Cardiac nonvalvular causes of death were due to heart failure (induding inability to wean from cardiopulmonary bypass), myocardial infarction, in-hospital arrhythmia, and sudden death. Noncardiac causes of death included trauma, malignancy, pulmonary insufficiency, aspiration pneumonia, renal fail-

Table IV. Risk factors associated with lower survival after St. Jude Medical valve replacement* Risk factor

p Value

Extensive CAD (triple vessel, left main) Advanced age (>70 years) Advanced NYHA class (III or IV) Cardiac rhythm (V Tach, sudden death)

<0.001 <0.001 <0.05 <0.05

CAD. Coronary artery disease: NYHA. New York Heart Association: V Tach. Ventricular tachycardia.

*Cox stepwise multivariate regression model.

ure, ruptured intraabdominal viscus, hepatic failure, and pancreatitis. Statistical methods. Tabular data are summarized by the mean and standard deviation for continuous variables and by percentages for categorical variables. Events were defined as death, valve-related complication, or either occurrence. Event rates are reported as the number of events per 100 patient-years at risk. Event rates for thromboembolism, valve thrombosis, and hemorrhage for periods before and after the change in anticoagulant recommendations (Oct. I, 1987) are compared by means of a Xl goodness of fit test. Actuarial curves were constructed by the life-table method, with all patients included at the initiation of the analysis. Survival probability, hazard functions, and corresponding standard errors were calculated

The Journal of

48

Czer et al.

.. .." s:

100

Thoracic and Cardiovascular Surgery

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80

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41 39 20

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Years 290 252 74

220 177 56

184 138 53

152 109 43

113 79 35

73 58 28

Fig. 3. Freedom from valve-related death according to valve position. shown actuarially by the lines at the topof the figure and referenced to the scale at the left. The yearly hazard rates ('lrjpt-yr) arc depicted as bar graphs and arc referenced to the scale at the right. There were no significant differences among the valve positions. Overall. XWlrr 4'7, of patients were free of valve-related causes of death at 9 years.

with the statistical software package BMDP PI L,21 with period cut points set at 30 days postoperatively and then arinually. Actuarial analysis was performed for subgroups based on selected stratification factors, and tests for equality among the actuarial curves were assessed by Breslow's version of the generalized Wilcoxon statistic. The univariate relationship between riskfactors and 30-day survival wasstudied by x2 tests, Fisher's exact test, and two-sample I tests. Correlates of long-term survival were studied by life-table analysis of those patients who survived beyond 30 dayspostoperatively. A Coxmodel survival analysis is used in a stepwise procedure?' to select the setof risk factors which best predict overall survival. Alltesting wasdone at the 0.05 significance level. Results Mortality and causes of death. The early (30-day) mortality rate was 8.3% overall and was higher after mitral (11.9%) than aortic (5.2%) or double (8.1%) valve replacement. There were three valve-related early deaths (Table Ill); two were due to rupture at the atrioventricular groove in patients with calcific mitral stenosis, and one was due to intracranial hemorrhage. Most early deaths (69%; 35/51) were from cardiac nonvalvular causes.

There were 18 valve-related late deaths, representing 14%of late deaths (Table III). Intracerebral (n = 10) or gastrointestinal (n = 2) hemorrhage in patients receiving warfarin anticoagulation accounted for 12 (67%) of late valve-related deaths. Five (28%) were due to stroke and one (6%) was due to valve thrombosis. A substantial proportion of late deaths were due to noncardiac causes (32%). The predominant causes of death were cardiac nonvalvular, constituting 53% oflate deaths (69/130). Survival. Actuarial survival was significantly lower for mitral valve recipients than for aortic or double valve recipients (p < 0.01, Fig. I). Survival rates were 71% ± 3%,69% ± 6o/r, and 59% ± 4% at 5 years and 51% ± 8%,47% ± 15%,and41% ± 6%at9yearsafter aortic, double aortic-mitral, and mitral valve replacement. respectively. Risk factors associated with poor long-term survival were identified after univariate screening by the lifetable method. These factors included age (greater than 70 years), preoperative NYHA functional class (Ill or IV), cardiac rhythm (ventricular tachycardia; sudden death), mitral lesion (regurgitation), aortic lesion

Volume 100

St. Jude Medical valve at 10 years 49

Number 1 July 1990

Table V. Valve-related complications Valve position ( 'omplicution

I lcmorrhagc lmbolism Vall'c thrombosis l.ndocarditi-, Paravalvular leak Hemolysis

lrosion Pannus formation Structural lailurc All complications

Aortic 2.X (27) :2.3 (22) 0.3 (3) 0.1 (I) 0.2 (2) 0.2 (2) 0.0 (0) 0.0 (0) 0.0 (0) 5.9 (57)

Mitral 2.1 1.6 0.3 0.4 0.4 0.0 0.3 0.0 0.0 4.9

(16) (12) (2) (3) (3) (0) (2) (0) (0) (3X)

Double 3.1 2.0 0.3 0.3 0.0 0.0 0.0 0.3 0.0 6.1

(9) (6) (I) (I) (0) (0) (0) (I) (0) ( IX)

All positions 2.6 2.0 0.3 0.2 0.2 0.2 0.1 0.0 0.0 5.6

(52) (40) (6) (5) (5) (2) (2) (I) (0) (113)

f),l!.l cvprc ......,.-. d n-, cv cnt-, per ]()() p.uicm-ycar-, of follow-up and (in parentheses) as number of events. Patient-years of follow-up were 967 for aortic, 771 for 11111LII. ;1I1d ~1>3 r~lr double valve replacement (total;;; :.!031 patient-years).

(stenosis), etiology of valve disease (ischemic), extent of associated coronary artery disease (triple vessel or left main), left ventricular ejection fraction (less than 55%), valve position (mitral), and other surgical procedures (coronary artery bypass grafting) (p < 0.01 for each). A Cox stepwise multivariate logistic regression model identified four independent predictors of lower actuarial survival rate: extensive associated coronary artery disease (p < 0.001), advanced age (p < 0.(01), advanced preoperative NYHA functional class (p < 0.05), and malignant ventricular arrhythmias (p < 0.05) (Table IV). All of the factors were patient-related; none was prosthesisrelated. The extent of associated coronary atherosclerosis was the strongest predictor of death and demonstrated a marked effect on operative mortality and actuarial survival (Fig. 2). With no associated coronary atherosclerosis, operative mortality rate was 3% and 9-year survival rate was 66% ± 7%; with triple vessel or left main coronary artery disease, operative mortality rate was 14%and 9-year survival rate was 29% ± 7% (p < 0.(01). Because a substantial portion of early and late deaths were noncardiac or cardiac nonvalvular, valve-related deaths were examined actuarially. No significant differences in the proportion of patients free of valve-related deaths were observed among the valve positions. At 9 years, 79% ± II % of aortic, 94% ± 3% of mitral, and 85% ± 7% of double valve recipients were free of valvular causes of death (Fig. 3). Valve-related complications. The most frequent complication was hemorrhage, which occurred at a linearized rate of 2.6%/pt-yr (Table V). Of 52 events, 13 (25%) resulted in death. There were no significant differences in the actuarial rates of freedom from hemorrhage by valve position(Fig. 4), with 86% ± 2% of patients free of hemorrhage at 9 years.

Embolism occurred at a linearized rate of 2.0%/pt-yr (Table V). Of 40 events, five (12.5%) were fatal. The actuarial freedom from embolism was 88% ± 3% after aortic, 92% ± 2% after mitral, and 89% ± 4% after double valve replacement at 9 years (p = NS, * Fig. 5). Overall, 90% ± 2% of patients were free of embolism at 9 years. Six valve thromboses (O.3%/pt-yr) were observed. All occurred in patients with suboptimal (prothrombin time less than 1.2 times control) or nonexistent dosages of warfarin, and one was fatal (17%). Actuarial screening of preoperative variables for their association with embolism or valve thrombosis demonstrated that the only preoperative risk factor was the presence of atrial fibrillation (p < 0.05). The linearized rates of hemorrhage, embolism, and valve thrombosis were compared before and after the target prothrombin time ratio for warfarin anticoagulation was reduced (from 1.5-2.5 previously to 1.5-2.0 currently) (Table VI). After the change, the rate of hemorrhage decreased by 44% (from 2.7% to 1.5%/pt-yr), whereas the rate of embolism and valve thrombosis increased by 14% (from 2.2% to 2.5%/pt-yr). Although not statistically significant because of the relatively short follow-up after the change (200 versus 1831 patient-years), the trend indicates a threefold greater reduction in hemorrhage rates compared with the small increase in the combined rate of embolism and valve thrombosis. No instances of valve thrombosis occurred after the change in recommendations. Paravalvular leak was documented in five patients (0.2%/pt-yr) and endocarditis in five patients (0.2%/ pt-yr). In the absence of paravalvular leak, clinically significant hemolysis occurred in two patients (0.1%/ pt-yr) and resolved spontaneously. An erosion into the atrioventricular groove developed in two patients, caus*NS = Not significant.

The Journal of

50

Thoracic and Cardiovascular Surgery

Czer et al.

100

--"":':::...

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---------------------------..... ...............

Q) 0)

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ns 80 s:

...... 0

E Q)

-...

20

% Free

30

--

60

days

100 100 ......... 100

--

J: 0

25

P = NS

40

5

9

years years

Aortic 0 Mitral. Aortic and Mitral 0

2 86,! 3 92~ 2 gO,! 3 83,! 6 77,! 8 89~

15

cfl.

a.

-::xJ l»

10

Q) Q)

L1.

J:

l» N l»

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cfl.

5

20

0

0 0

2

3

175 133 50

140 103 40

1

4

5

6

7

8

9

10

37 38 17

24 29 12

13 25 4

3 6 2

1

Years 290 252 74

213 176 55

101 74 31

65 56 24

Fig. 4. Freedom from hemorrhage in aortic, mitral, and double valve recipients. No significant differences in rates of hemorrhage were observed among the valve positions. Overall, 86% ± 2% of patients were free of hemorrhage at 9 years.

Table VI. Rates of hemorrhage. embolism. and valve thrombosis before and after change in anticoagulation recommendations * Complication

Before

After

Change

Hemorrhage Embolism, valve thrombosis

2.7 (49) 2.2 (41)

1.5 (3) 2.5 (5)

-44(if +14(if

• Anticoagulant recommendation changed Oct. I. 19X7. Data arc expressed as events per 100 patient-year- of follow-up and (in parentheses) as number ofevents. Patient-years of follow-up were IXJ1 before and .::!OO after change in recommcnd.uions,

ing death within 30 days of operation In both instances. In total, 113 valve-related complications occurred (5.6%/pt-yr) (Table V). When examined actuarially, there were no statistically significant differences in freedom from all valve-related complications among valve positions (Fig. 6), although there was a trend toward a higher rate of complications in double valve recipients. Reoperations. Reoperation was performed for four paravalvular leaks caused by endocarditis, one additional case of endocarditis not associated with para valvular leak, two valve thromboses, and one subaortic ring because of

pannus formation (causing abnormal leaflet motion), for a total of eight instances (O.4%/pt-yr). All except one patient survived reoperation. Functional class. The NYHA functional class was III or IV in 94% of patients preoperatively (Table I); 6 months postoperatively, 86% were in functional class lor II, and 14% were in class III or IV (p < 0.01). The NYHA class was compared over three time Periodspostoperatively: at 6 months, I year, and 5 years after operation (Fig. 7). NYHA class I was maintained in 60%, 56%,and 55% of patients at these time intervals. Class IV symptoms occurred in 4%, 5%, and 5% of patients during the same time period, respectively. Discussion This study demonstrates that the St. Jude Medical valve continues to be a durable prosthesis, with no structural failures occurring up to 10 years postoperatively. The St. Jude Medical valve exhibited a low rate of embolic complications (2.0%/pt-yr); at 9 years, 90% ± 2% of patients remained free of emboli (Table V and Fig. 5). We have previously demonstrated that thromboembolic risk was lowest in patients maintained on warfarin anticoagulation and that a higher risk is

Volume 100 Number 1

St. Jude Medical valve at 10 years 5 1

July 1990

100

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- - 100 88~ 3 88.:!: 3 - - 99.:!: 1 92.:!: 2 92.:!: 2 ......... 100 89.:!: 4 89.:!: 4

60

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30

40

Q) Q)

... -...:.:.:.: .7.7.7.-:.:.:...

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15

--

Aortic 0 - - Mitral. ......... Aortic and Mitral 0

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:JJ

....

-D)

10

(1)

cf.

0

5

0

1

2

3

4

5

6

7

8

9

10

35 38 19

23 28 13

12 24 5

3 5 2

1

0

Years .........

290 252 74

216 177 54

178 135 48

144 105 38

104 75 31

66 56 25

Fig. 5. Freedom from embolism. There were no significant differences by valve position; 90% ± 2% of all patients were free of embolism at 9 years.

imparted in patients maintained on antiplatelet drugs or no antithrombotic therapy. I g It is interesting to note that all cases of valve thrombosis (n = 6; Table V) occurred in patients with subtherapeutic (prothrombin time < 1.2 times control) or nonexistent dosages of warfarin. An additional risk factor for embolism and valve thrombosis identified in the current study was the presence of atrial fibrillation. Thus warfarin continues to be recommended in all patients. Dipyridamole (300 to 400 mg daily) can be added for patients at increased risk for thromboembolism,such as those with atrial fibrillation. Other high-risk categories may include patients with left atrial thrombus at operation, a prior history of embolism, or marked enlargement of the left atrium. Io. 22. 23 Young children (less than 5 years old) may be managed with antiplatelet therapy alone" or with warfarin monitored by a fingerprick technique." The most frequent valve-related complication was hemorrhage, which occurred at a rate of 2.6%/pt-yr (Table V). Thirteen (25%) of 52 events were fatal, and these deaths accounted for 62% of all valve-related deaths (13/21; Table III). Thus warfarin-related hemorrhage has been the major contributor to valve-related morbid-

ity and mortality in our series. With the recognition that anticoagulation regimens based on currently available prothrombin assays may lead to excessive anticoagulation,16-lg we lowered the upper limit of our target prothrombin time ratio from 2.5 to 2.0 in October 1987. Importantly, after the target prothrombin time ratio was lowered, the linearized rate of hemorrhage decreased by 44% (from 2.7% to 1.5%/pt-yr) (Table VI). At the same time, the combined rate of embolism and valve thrombosis increased slightly (from 2.2 to 2.5%/pt-yr, a 14% change); however, the overall rate of hemorrhage, embolism, and valve thrombosis was lower after the change in anticoagulation recommendations (4.0%/ptyr) than before (4.9%/pt-yr). Even lower target prothrombin time ratios (1.3 to 1.5) have been used for the St. Jude Medical valve,19 resulting in comparable linearized rates of hemorrhage (1.3%/pt-yr) without an increase in thromboembolic complications. Thus it is clear that less intense warfarin regimens can reduce hemorrhagic risk while maintaining thromboembolic protection. Spontaneous fluctuations in the prothrombin time are a well-described occurrence in patients maintained on

52

The Journal of Thoracic and Cardiovascular

Czer et al.

Surgery

100

- AortlcO - - Mitral. ......... Aortic and Mitral

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Fig. 6. Freedom from all valve-related complications, according to valve position. There was a slight trend toward more frequent complications in double valve recipients, which was not statistically significant.

stable dosages of'warfarin.P Unfortunately, these fluctuations may cause significant shortfalls or excesses in anticoagulation that, in turn, increase the risk of adverse clinical events such as thrombosis, embolism, or hemorrhage. Frequent monitoring of the prothrombin time by venipuncture has traditionally been necessary to avoid anticoagulation-related complications. Recently, a portable prothrombin time device has become available that uses a single drop of capillary whole blood obtained by fingerstick (Coumatrak, Du Pont Company, Wilmington, Del.). A randomized, prospective study has demonstrated that use of a portable prothrombin time device by patients at home is feasible, provides accurate measurements, and achieves better anticoagulation control than standard outpatient care." The use of such a device may be especially appropriate in patients with mechanical prosthetic valves because the improved anticoagulation control may translate into a reduced occurrence of adverse clinical events, although this has not yet been proved. Most deaths in this series were not from prosthesis-related causes, which constituted 12% of deaths; indeed, 88% ± 4% of patients remained free of valve-related causes of death after 9 years (Fig. 3). Rather, most deaths (88%; 159/181) were due to nonvalvular causes (Table III).

The strongest risk factor for death was the presence and extent of associated coronary atherosclerosis (Table IV and Fig. 2). We have previously demonstrated the adverse impact of coronary artery disease on early mortality and late survival after mitral 27 and aortic-" valve replacement. With concomitant left main or triple vessel coronary artery disease, the operative mortality rate after St. Jude Medical valve replacement was 14% and thes-year survival rate was 29% ± 7%. Conversely, without associated coronary artery disease, the operative mortality rate was 3% and the 9-year survival rate was 66% ± 7% (p < 0.(01). Other independent risk factors for death were advanced age (greater than 70 years), advanced preoperative NYHA functional class (III or IV), and the presence of malignant ventricular ectopy (ventricular tachycardia, history of sudden death) (Table IV). Thus the relatively high operative mortality (8.3%) and low 9year survival rates (Fig. 1) reflect the inclusion of high-risk patients, such as those with ischemic heart disease, left ventricular dysfunction, serious ventricular arrhythmias, and the elderly. Reported series without a large proportion of high-risk patients may be expected to have a lower operative mortality and a higher survival rate. 14. 15

Volume 100 Number 1

St. Jude Medical valve at 10 years 53

July 1990

60 r-----r--..,.--=~-'"""'_ 50 40 30

20 10

Fig. 7. NYHA functional class before and at 6 months, I year, and 5 years after operation. There was no significant change in the profile of functional class after the initial improvement seen at 6 months; the improvement in functional class was maintained up to 5 years postoperatively. The vertical axis depicts the percentage of patients in each functional class during the specified time periods.

The functional status of surviving recipients of the 81. Jude Medicalvalve was favorable when compared with the status before the operation. Whereas 94% were in class III or IV preoperatively, 86% achieved class I or II by 6 monthspostoperatively. Furthermore,the profile did not changesignificantly at 1 year or 5 years after operation (Fig. 7). Thus functional improvement appeared to besustained to at least 5 yearspostoperatively, perhapsin part because of the favorable hemodynamic characteristics of the valve. 1-10 We thank Sharo Raissi, MD, of the Department of Thoracic and Cardiovascular Surgery; John Bussell, MD, Arnold Friedman, MD, Harley Geller, MD, and Erroll Hackner, MD, of the Department of Anesthesiology; and Myles E. Lee, MD, whose patients were included in this study. Special thanks to Denise Arias for manuscript preparation.

3.

4.

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REFERENCES I. Gray R, Chaux A, Matloff J, Raymond M. Early postoperative hemodynamic comparison of St. Jude cardiac prostheses and porcine xenografts, at rest and with stress. Circulation 1979;59,60(Pt 2):11222. 2. Emery RW, Demetre M, Nicoloff OM. St. Jude Medical

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8.

cardiac valve prosthesis. J THORAC CARDIOVASC SVRG 1979;78:269-76. Gabbay S, Yellin EL, Frishman WH, Frater RWM. In vitro hyrodynamic comparison of St. Jude, Bjork-Shiley and Hall-Kaster valves. Trans Am Soc Artif Intern Organs 1980;26:231-6. Wortham DC, Tri TB, Bowen TE. Hemodynamic evaluation of the St. Jude Medical valve prosthesis in the small aortic anulus. J THORAC CARDIOVASC SVRG 1981;81:61520. Yoganathan AP, Chaux A, Gray RJ, DeRobertis M, Matloff JM. Flow characteristics of the St. Jude prosthetic valve: an in vitro and in vivo study. Artif Organs 1982;6:288-94. Bruss KH, Reul H, Van Gilse J, Knott E. Pressure drop and velocity fields at four mechanical heart valve prostheses: Bjork-Shiley standard, Bjork-Shiley concave-convex, HallKaster and St. Jude Medical. Life Support Syst 1983;1:322. Horstkotte 0, Haerten K, Seipel L, et al. Central hemodynamics at rest and during exercise after mitral valve replacement with different prostheses. Circulation 1983; 68(Pt 2):11161. Yoganathan AP, Chaux A, Gray RJ, et al. Bileaflet, tilting

The Journal of Thoracic and Cardiovascular Surgery

5 4 Czer et al.

disc and porcine aortic valve substitutes: in vitro hydrodynamic characteristics. J Am Coli Cardiol 1984;3: 313-20. 9. Gray RJ, Chaux A, Matloff JM, et al. Bileaflet, tilting disc and porcine aortic valve substitutes: in vivo hydrodynamic characteristics. J Am Coli CardioI1984;3:321-7. 10. Czer LSC, Matloff J, Chaux A, DeRobertis M, Yoganathan A, Gray RJ. A 6 year experience with the St. Jude Medical valve: hemodynamic performance, surgical results, biocompatibility and follow-up. J Am Coli Cardiol 1985;6:904-12. II. Chaux A, Gray RJ, Matloff JM, Feldman H, Sustaita H. An appreciation of the new St. Jude valvular prosthesis. J THORAC CARDIOVASC SURG 1981;81:202-11. 12. Nicoloff DM, Emery RW, Arom KV, et al. Clinical and hemodynamic results with the St. Jude Medical cardiac valve prosthesis. J THORAC CARDIOVASC SURG 1981; 82:674-83. 13. Chaux A, Czer LSC, Matloff JM, et al. The St. Jude Medical bileaflet valve prosthesis. J THORAC CARDIOVASC SURG 1984;88:706-17. 14. Baudet EM, Oca CC, Roques XF, et al. A 5112 year experience with the St. Jude Medical cardiac valve prosthesis. J THORAC CARDIOVASC SURG 1985;90:137-44. 15. Duncan MJ, Cooley DA, Reul GJ, et al. Durability and low thrombogenicity of the St. Jude Medical valve at 5-year follow-up. Ann Thorac Surg 1986;42:500-5. 16. Hirsch J, Deykin D, Poller L. "Therapeutic range" for oral anticoagulant therapy. Chest 1986;89(February suppl): IIS-5S. 17. Stein PD, Collins JJ, Kantrowitz A. Antithrombotic therapy in mechanical and biological prosthetic heart valvesand saphenous vein bypass grafts. Chest 1986;89 (February suppl):46S-53S. 18. Czer LSC, Matloff JM, Chaux A, DeRobertis M, Stewart ME, Gray RJ. The St. Jude valve: analysis of thromboembolism, warfarin-related hemorrhage, and survival. Am Heart J 1987;114:389-97. 19. KopfGS, Hammond GL, Geha AS, Elefteriades J, Hashin SW. Long-term performance of the St. Jude Medical valve: low incidence of thromboembolism and hemorrhagic complications with modest doses of warfarin. Circulation I987;76(Pt 2):III 132-6. 20. Chaux A, Blanche C . Technical aspects of valvular replacement with the St. Jude prosthesis. J Cardiovasc Surg 1987;28:363-8. 21. BMDP Statistical Software Manual, Berkeley: University of California Press, Vol 2, 1988. 22. Chesebro JH, Fuster V, Elveback LR, et al. Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic valve replacement: danger of aspirin compared with dipyridamole. Am J CardioI1983;51:1537-41. 23. Sullivan JM, Harken DE, Gorlin R. Pharmacologic control of thromboembolic complications of cardiac valve replacement. N Engl J Med 1971;284:1391-4. 24." Schaffer MS, Clarke DR, Campbell DN, Madigan CK, Wiggins JW, Wolfe RR. The St. Jude Medical cardiac

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valve in infants and children: role of anticoagulant therapy. J Am Coli Cardiol 1987;9:235-9. Butchart EG, Lewis PA, Grunkemeier GL, Kulatilake N, Breckinridge 1M. Low risk of thrombosis and serious embolic events despite low-intensity anticoagulation: experience with 1,004 Medtronic-Hall valves. Circulation 1988;78(Pt 2):166-77. White RH, McCurdy SA, von Marensdorf H, Woodruff DE, Letgoff L. Home prothrombin time monitoring after the initiation of warfarin therapy: a randomized, prospective study. Ann Intern Med 1989;111:730-7. Czer LSC, Gray RJ, DeRobertis MA, et al. Mitral valve replacement: impact of coronary artery disease and determinants of prognosis after revascularization. Circulation 1984;70(Pt 2):1198-207. Czer LSC, Gray RJ, Stewart ME, DeRobertis M, Chaux A, Matloff JM. Reduction in sudden late death by concomitant revascularization with aortic valve replacement. J THORAC CARDIOVASC SURG 1988;95:390-401.

Discussion Dr. Bradley J. Harlan (Sacramento. Calif). I congratulate Dr. Czer and his colleagues on this report covering a decade of their experience with the St. Jude Medical valve. This report adds to their previous contributions regarding the St. Jude Medical valveand, with other reports, continues to esta blish that the St. Jude Medical valve has excellent hemodynamics, a low incidence of thromboembolism in properly anticoagulated patients, and so far is free from structural failure. Dr. Czer's report also touches on some unresolved questions regarding the St. Jude Medical valve, particularly its small, but present, predisposition to thrombosis and the question of the. ideal level of anticoagulation. I would like to confine my comments and questions to these two areas. First, you stated that valve thromboses all happen in patients with inadequate anticoagulation. Are there other factors that may have contributed, such as the orientation of the valve? What is the preferred orientation at the present time in the aortic and mitral positions? Dr. Czer. We could not find any particular orientation or valve position that predisposed to valve thrombosis. In the aortic position, we currently place one pivot guard against the interventricular septum and the other between the noncoronary and left coronary cusps. In the mitral position the pivot guards are oriented in an anti anatomic axis perpendicular to the mitral commissure. Very early in our series, other orientations were used; nevertheless, these orientations did not produce a higher rate of valve thrombosis. In aortic, mitral, and double aorticmitral recipients, the rates of valve thrombosis have been identical (0.3%jpt-yr). Dr. Harlan. With the growing propensity to leave part or all of the mitral valve apparatus in place, is there any concern about any impingement on valve leaflet motion, or do the surgeons feel comfortable with leaving the mitral valve in place with the use of the St. Jude Medical prosthesis? Dr. Czer. A concern of ours has been the potential for interference of residual mitral leaflet tissue with prosthetic leaflet motion. From the beginning we have been meticulous about removing all tissue from the immediate vicinity of the prosthetic valve, including valvular tissue itself, especially in the mitral

Volume 100 Number 1 July 1990

position. There are only two patients in our series in whom we have left the posterior mitral leaflet intact. Dr. Harlan. You concluded, or suggest, that a target prothrombin ratio of 2.0 is better than 2.5. Do your data support this suggestion or this conclusion? Is it not possible that those patients who had hemorrhagic complications actually had prothrombin ratios well in excess of 2.5? In fact, do you know what the prothrombin time ratio in these patients was when the hemorrhagic complication occurred? Dr. Czer. Initially, our target prothrombin time ratio was between 1.5 and 2.5; now it is between 1.5 and 2.0. Although data directly confirming achievement of these target ranges are

St. Jude Medical valve at 10 years 55

not currently available for our entire patient population, we have found prothrombin time ratios to be within the desired range in a small, random sample of patients. Documentation of the prothrombin time immediately before a hemorrhagic event is incomplete for our patients. There is now substantial evidence in the literature that a prothrombin time ratio between 2.0 and 2.5 leads to a high rate of clinically significant bleeding. Dr. Harlan: Nevertheless, there are series of patients in the literature who, in fact, do fit into your higher range and yet do not have the high prevalence of hemorrhagic complications that you describe.