Chronic Intravascular Hemolysis After Aortic Valve Replacement With lonescu-Shiley Xenograft: Comparative Study With Bjork-Shiley Prosthesis
PEDRO USAF, WILSON
R. FEBRES-ROMAN, MC* C. BOURG,
RICHARD
A. CRONE,
RICHARD
C. DAVIS,
LTC, MC TROY H. WILLIAMS, Aurora,
MD, MD, Jr., MD,
MD, MAJ,
MC
MAJ, MD, COL,
MAJ,
MC
PhD, MC
Colorado
Twenty patients with a prosthetic valve (lonescu-Shiley or Bjork-Shiley) in the aortic poettion were studied for evidence of intravascular hemolysis. Serum lactic dehydrogenase and serum haptoglobtn levels were used as the most sensitive indicators of hemolysis. Elevated concentrations of lactic dehydrogenase were found in all 10 patients wtth an lonescu-Shlley prosthesis (mean 402 IU/IRer) and in 7 of 10 patients with a Bjok-Shiley prosthesis (mean 234 Wltter). The mean serum haptogtebtt was 15 mg/dl (range 10 to 28) in patients with the lonescu-Shiley valve and 96 mg/dl (15 to 284) for those with the Bjok-Shiley valve. This study indicates the presence of chronic intravascular hemotysis in patients with the lonescu-Shiley aortic valve. The increase in lactic dehydrogenase was significantly greater in patients with the lonescu-Shiley prosthests than in those with the Bjork-Shiley prosthesis, indicating a sltghtly shorter red cell life span in the former group.
Intravascular hemolysis in patients with prosthetic heart valves has been recorded for ball valve and disc prostheses.‘-* The newer tissue valves have been the subject of fewer studies.5-7 Recent repontss1° have stated that the Ionescu-Shiley pericardial xenograft does not cause detectable hemolysis. In contrast, well have found evidence of hemolysis associated with this prosthesis in the mitral position. In this study we attempted to assess the incidence and severity of hemolysis in 10 patients with the Ionescu-Shiley xenograft in the aortic position. The results were compared with those found in 10 patients with a Bjork-Shiley aortic valve disc prosthesis. Methods
From the Cardiology and Hematology Sections, Department of Medicine, Fitzsimons Army Medical Center, Aurora, Colorado. The opinions expressed herein are the private views of the authors, and do not reflect the views of the Department of the Army or the Department of Defense. Manuscript received April 29, 1980, accepted May 29, 1980. present address and address for reprints: Pedro R. Febres-Roman, MD, Cardiac Non-lnvasive Diagnostic Laboratory, Cardiopulmonary Service, Wright-Patterson Air Force Base, Ohio 45433. l
Patients: Twenty patients (14 men and 6 women) who had undergone aortic valve replacement were studied; of these, 10 patients had valve replacement with the Ionescu-Shiley xenograft and 10 with the Bjork-Shiley prosthetic valve. In the group with the Ionescu-Shiley valve, the hematologic studies were performed at a mean interval of 10.6 months (range 3 to 16) after aortic valve replacement; five valve sizes (anulus diameter 19,21,23,25 and 27 mm) were used. The mean age of the patients in this group was 53.8 years (range 20 to 72). The group with the Bjork-Shiley valve was studied at a mean interval of 31 months (range 3 to 48) after operation; three valve sizes (anulus diameter 21,23 and 25 mm) were studied. The mean age of the patients in this group was 58.5 years (range 47 to 65). Of the 10 patients with an Ionescu-Shiley valve, 9 underwent postoperative hemodynarnic and angiographic investigations; 8 of the 9 had a competent valve, and all had a small transvalve gradient. One patient had a grade I/IV paravalve leak. Laboratory studies: To assess hemolysis, the following laboratory tests were performed: a complete blood count with reticulocyte count, platelet count, red cell indexes and examination of the blood smear. Other studies included determination, by standard methods, of serum haptoglobin, serum lactate dehydro-
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TABLE I Comparison of Hematologic Variables in IO Patients With the lonescu-Shlley and 10 With the Bjork-Shiley Aortic Prosthesis Serum LDH (Wliter)
SGOT (IMiter)
Serum Haptoglobin (mg/dl)
Hemoglobin (g/100 ml)
Hematocrit (%)
Reticulocyte Count ( % )
go-215
10-50
170-300
12.5-18
38 to 52
<2
402 294-580
2,“_‘8
Id-528
13.8 12.5-16
8Y6
234 178-287 <0.05
243-137 NS
96 15-284 <0.05
14.5 13.1-16 NS
3E47 NS
Normal range lonescu-Shiley Mean Range Bjork-Shiley Mean Range p value
LDH = lactic dehydrogenase; n = number; NS = not significant; p = probability (p <0.05 transaminase.
genase with isoenzymes, serum glutamic oxaloacetic transaminase @GOT) and total bilirubin concentration. Serum iron, total iron-binding capacity, iron saturation, urine hemosiderin were also measured and Coombs’ test was performed. Clinical features: Clinical assessment of all patients, together with hemodynamic and angiographic evaluation (9 of the 10 patients with an Ionescu-Shiley valve), revealed no apparent contributory cause of the hemolysis, with the exception of a mild grade (I/IV) paravalve leak in one patient with the Ionescu-Shiley valve; in addition, one patient with the latter valve had a sinus of Valsalva aneurysm repaired with
7-7 0 x
= significant); SGOT = serum glutamic oxaloacetic
Serum lactic dehydrogenase: Laboratory data obtained from patients with the two types of aortic valve prosthesis are summarized in Table I and Figure 1. The mean value for serum lactic dehydrbgenase in patients with an Ionescu-Shiley valve (402 IU/liter) was significantly (p cO.05) greater than the mean value for patients with a Bjork-Shiley valve (234 IU/liter). In the latter group, lactic dehydrogenase values were only slightly higher than the normal range. The highest value (580 IU/liter) was obtained in a patient with an Ionescu-Shiley valve who had the mild paravalve leak. Serum haptoglobin: Reduced serum haptoglobin was found in 100 percent of patients with an IonescuShiley prosthesis (less than 50 mg/dl in all cases), but in only 80 percent of patients with a Bjork-Shiley valve (two patients had normal values). Mean values for haptoglobin were lower than normal in both patient
infarction by clinical or electrocardiographic evidence. The patients showed no evidence of autoimmune disease (negative Coombs’ test). Hence, any intravascular hemolysis was wholly attributable to the prosthesis in most patients. Student’s t test was used for statistical evaluation of the results. Probability (p) values greater than 0.05 were considered not statistically significant.
.
0.8 0.5-1.0 <0.05
Results
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FIGURE 1. Plot diagram showing the relation between serum lactic dehydrogenase (LDH) and haptoglobin values in patients with the lonescuShiley or Bjork-Shiley prosthesis. The horlzonlsi Interrupted fine marks the upper normal range for lactic dehydrogenase, and the vertical lntem#ed line marks the lower normal range for haptoglobin.
IONESCU-SHILEY
groups (Table I). In patients with the Ionescu-Shiley valve, elevated lactic dehydrogenase values were always associated with reduced haptoglobin. In the group with the Bjork-Shiley valve haptoglobin was reduced in some patients in spite of normal lactic dehydrogenase values (Fig. 1). Relation to valve size: The relation between valve size and values for lactic dehydrogenase and serum haptoglobin is shown in Figures 2 and 3, respectively. The degree of hemolysis as measured by either value apparently had no direct relation to valve size in any of the two prostheses evaluated. Other signs of hemolysis: Hemoglobin concentrations (Table I) were definitely but not significantly lower in patients with an Ionescu-Shiley prosthesis. Reticulocyte counts were raised in four patients with an Ionescu-Shiley prosthesis (2.1, 2.8, 3.0, and 5.6, respectively). In the group with the Bjork-Shiley prosthesis hemolysis was so slight that reticulocyte counts were normal in all. One patient with an Ionescu-Shiley valve and a mild paravalve leak had hemosiderinuria. This patient also had the highest lactic dehydrogenase value (580 IU/liter). Bilirubin values were normal in all patients except one with an Ionescu-Shiley valve who had a marginally raised level. Other laboratory values: The Coombs’ test was negative in all patients in both groups. This finding suggests that no immune mechanism was involved in the hemolytic process. Serum glutamic oxaloacetic transaminase, serum iron, total iron binding capacity, peripheral blood smear and platelets were normal in patients in both groups. Discussion Hemolysis as a complication of valve replacement: Chronic intravascular hemolysis is a well-known complication of valve replacement and is probably related to the mechanical design of the prosthesis itself.12 Measurement of serum lactic dehydrogenase (LDH, red cell isoenzyme) is a sensitive method of estimating intravascular hemolysis, and the level correlates well with the shortening of erythrocyte survival time.13 It was elevated in all patients with an Ionescu-Shiley prosthesis, but in only two thirds of those with a BjorkShiley valve. In patients with the former valve, most lactic dehydrogenase values were in the range of 300 to 500 IU/liter, indicating a slightly or only moderately reduced life span of erythrocytes.1” Serum haptoglobin levels have been used in previous reports; as another index of hemolysis. In our series the haptoglobin levels were greatly decreased in all patients with the Ionescu-Shiley valve and less markedly decreased in those with the Bjork-Shiley valve. A positive direct Coombs’ test has been reported in patients after heart valve replacement. It has been suggested that an immune mechanism may be involved in some cases of hemolysis after valve replacement.14 In our study the direct Coombs’ test was negative in all cases. Therefore, it is unlikely that an immune mechanism played a role in the hemolysis detected in our series.
<
XENOGRAFT AND HEMOLYSIS-FERRES-ROMAN
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ET AL.
. 300
x
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200
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-
100
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21
23
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(mm)
FIGURE 2. Serum lactic dehydroganase (LDH) values related to valve size and type. The shad4 area shows the normal range. Valve size is indicated by the valve number given by the manufacturer.
Role of size and type of valve prosthesis: There has been controversy about whether prostheses of the same type cause different degrees of hemolysis in the aortic and mitral position.12J5 Well previously found that the Ionescu-Shiley prosthesis in the aortic position caused slightly greater hemolysis than the same valve in the mitral positon. Similar findings have been reported with the Starr-Edwards prosthesis2J5 Hemolysis has been reported to be dependent on the size of the prosthesis. 4~16Other investigators’ have reported no correlation between the degree of hemolysis
0 0
150-
73 0
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125-
I” 100 75 -
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21
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25
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FIGURE 3. Serum haptoglobin values related to valve size and type. Conventions as in Figure 2.
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and the valve size. We found no direct relation between lactic dehydrogenase, haptoglobin and valve size (Fig. 2 and 3). There is conflicting evidence concerning the value of increased serum lactic dehydrogenase as an indicator of a paravalve leak. ly7In our series, the highest value for lactic dehydrogenase was found in a patient with the only Ionescu-Shiley valve with a mild paravalve leak. Nevertheless, our data are inconclusive in this respect. Implications: This hematologic study was carried out at a relatively short postoperative time interval in the group with the Ionescu-Shiley valve (mean 10.6
months). Investigators with a longer observation period of patients with other types of prostheses have reported a regression of hemolysis due to endothelialization of the valve structures.7 If this interpretation is correct, with time one would observe a lesser degree of erythrocyte destruction with the Ionescu-Shiley xenograft than that indicated by our data. In conclusion, this study has indicated the presence of chronic, mild intravascular hemolysis in patients with the Ionescu-Shiley prosthesis. The findings are suggestive of a significantly greater incidence and degree of hemolysis in patients with this prosthesis than in those with the Bjork-Shiley prosthesis.
References 1. Nltter-Hauge S, Sommerfelt SC, Hall KV, Froysaker T, Efskln L. Chronic intravascular hemolysis after aortic disc valve replacement. Br Heart J 1974;36:781-5. 2. Falk RH, Mackinnon J, Walnscoat J, Mellklan V, Blgnell AHC. Intravascular hemolysis after valve replacement: comparative study between Starr-Edwards (ball valve) and Bjork-Shiley (disc valve) prosthesis. Thorax 1979;34:748-8. 3. Bjork OV, Henze A, Carlstrom A. Hematologic evaluation of the Bjork-Shiley tilting disc valve prosthesis in isolated aortic valvular disease. Stand J Thorac Cardiovasc Surg 1974;8:12-30. 4. Dale J, Blybre E. Intravascufar hemolysis in the late course of aortic valve replacement. Relation to valve type, size and function. Am Heart J 1978;98:24-30. 5. Rhodes OR, McIntosh CL. Evaluation of hemolysis following replacement of atrioventricular valves with porcine xenograft (Hancock) valves. J Thorac Cardiovasc Sure 1977;73:312-5. 8. Myers TJ,‘HIld DH, Rlnakll MJ. Hernolytic anemia associated with heterograft replacement of the mitral valve. J Thorac Cardiovasc Surg 1978;78:214-5. 7. Dave KS, Yadan CK, Pakrasbl BC, Roberts BE, lonescu MI. Chronic hemolysis following fascia lata and Starr-Edwards aortic valve replacement. Circulation 1972;48:240-9. 8. lonescu Ml, Tandon AP, Mearns AJ, Roesler MF. Long-term clinical and hemodynamic evaluation of the lonescu-Shiley pericardial xenograft heart valve (abstr). Thorax 197934132.
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9. Tandon AP, Smith DR, Whltaker W. lonescu MI. Long-term hemodynamic evaluation of aortic pericardial xenograft. Br Heart J 1978;49:802-7. 10. Tandon AP, Bengupta SM. Lukacs L, lonescu Ml. Long-term clinical and hemodynamic evaluation of the lonescu-Shiley pericardial xenograft and the Eraunwald-Cutter and Bjork-Shiley prostheses in the mitral position. J Thorac Cardiovasc Surg 1978;78:783-70. 11. Febres-Roman PR, Haas JM, Cowen GO. Hemodynamic assessment of the lonescu-Shiley pericardfal xenograft in the mitral position. Cathet Cardiovasc Diagn 1980;8:233-45. 12. Crexells C, Aerkhlde N, Bomy Y, Lepase G, CarnPeau L. Factors influencing hemolysis in valve prosthesis. Am Heart J 1972;84: 181-70. 13. Mylue E, Rasmussen K. Andemen A. Serum lactic dehydrogenase activity in patients with prosthetic heart valves: a parameter of intravascular hemolysis. Am Heart J 1970;80:483-8. 14. Plrofsky 8, Sutherland DW, Starr A, Griswold HE. Hemolytic anemia complicating aortic valve surgery: an autoimmune syndrome. New Engl J Med 1985;272:235-8. 15. Yarmb MH, Keeling DH. Chronic hemolysis following insertion of ball valve prostheses. Br Heart J 1988;30:878-8. 18. Myhre E, Dale J, Rasmussen K. Erylhrocyte destruction in different types of Starr-Edwards aortic ball valves. Circulation 1970;42: 515-20.
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