Thromboembolism After Beall Valve Replacement of the Mitral Valve Neal W. Salomon, M.D., Peter P. Steele, M.D., a n d Bruce C. Paton, M.D. ABSTRACT A series of 76 isolated mitral valve replacements with the Beall valve is reported. A perioperative mortality of 3.5% (3 patients) and a late mortality of 6.8% (5 patients) was obtained Thromboembolism occurred in 4 patients (5.2%). In a separate study, platelet survival times were determined in 17 patients with Beall valves by using chromium 51-labeled autologous platelets. Six patients had had thromboembolic (TE) episodes; the remaining 11 had not. The normal platelet survival time was > 3.3 days. Patients with TE had shortened platelet survival times (mean 2.8 f 0.11 days) which were significantly less ( p < 0.01) than those of patients without T E (mean 3.4 & 0.13 days). The incidence of TE, which is associated with shortened platelet survival time, is low with Beall mitral valves. Prognostic and therapeutic consi,derations are discussed.
I
n 1967 Beall [Z, 31 introduced a Dacron velour-covered Teflon-disc mitral valve prosthesis which several recent studies [4, 10, 161 have shown to be comparable, if not superior, to other existing mitral valve designs in terms of early and late mortality and low incidence of thromboembolization. Beall reported a 4.5% total incidence of thromboembolic episodes with only a 3.6% incidence of late emboli [4]. Previous studies have described hemodynamic results after Beall valve replacement associated with symptomatic and functional postoperative improvement [13-1 5, 201. Nevertheless, symptomatic improvement is often accompanied by persistent postoperative transvalvular pressure gradients and elevated mean pulmonary artery and pulmonary artery wedge pressures, all of which significantly increase during exercise [ 15, 191. T h e present study is concerned with late mortality and morbidity in a consecutive series of 76 patients who survived isolated mitral valve replacement with a Beall valve prosthesis. T h e efficacy of and need for anticoagulation continues to be a matter for discussion. Beall [4] has found that there is little or no difference in the incidence of emboli between patients receiving anticoagulants and those not receiving them. Others have come to the same conclusion with difl'erent types of valves, which suggests that whatever factors are involved are not seriously influenced by warfarin anticoagulation. Weily, Steele, and Genton [24] studied platelet survival times in 9 patients with Beall valves and found the platelet survival times to be almost normal. Similar findings in patients with other types of valves were From the Departments of Medicine and Surgery, University of Colorado Medical Center, Denver, Colo. Accepted for publication Aug. 8, 1974. Address reprint requests to Dr. Paton, Department of Surgery, University of Colorado Medical Center, 4200 E. Ninth Ave., Denver, Colo. 80220. VOL.
19, NO.
1, JANUARY,
1975
33
SALOMON, STEELE, AND PATON
associated with a low incidence of thromboembolism [22]. Prognostic and therapeutic implications of these findings are discussed in this paper.
Clinical Material and Methods Between August 29, 1967, and March 28, 1973 (5 years 7 months), 76 mitral valves were replaced by Beall valves in patients with isolated mitral disease at the University of Colorado Medical Center and the Denver Veterans Administration Hospital. Only patients undergoing isolated mitral valve replacement are included in this study; 28 additional patients operated upon during the same period for either double-valve replacement or valve replacement combined with coronary artery bypass grafting were excluded. All patients were considered to be in N.Y.H.A. Class 111 or IV preoperatively, and no patients were denied operation because of terminal cardiac dysfunction. A total of 50 small (including 4 pediatric), 19 medium, and 7 large Beall valves were inserted. There were 48 female and 28 male patients ranging from 10 through 63 years with a mean age of 47. Standard cardiopulmonary bypass procedures were employed, using disposable Travenol oxygenators primed with lactated Ringer’s solution. Throughout the 5S-year period 20 patients have been lost to follow-up at various intervals postoperatively and have been considered only for as long as appropriate follow-up contact was made. Many patients were not local residents but came from several neighboring states; hence only indirect contact through their local referring physician could be made. Accurate evaluation of which patients were adequately maintained on oral anticoagulants was difficult to obtain. In a separate study, platelet survival times were determined in 17 patients (12 men, 5 women), all of whom had a Teflon disc valve. None had a valve with a pyrolytic carbon disc. Nine of these patients are included in the operative follow-up series, and 8 of the 17 were referred specifically for platelet studies. Six of the 17 patients (including 2 from the operative series) examined for platelet survival times suffered strokes. T h e remaining 11 patients had no evidence of thromboembolism. Platelet survival time was measured by labeling autologous platelets obtained from 450 ml of blood with 100 to 150 pCi of chromium 51 [l]. T h e labeled platelets were reinfused and samples obtained 2 to 3 hours later and then daily for 7 days. T h e platelet button was counted, and a single exponent fitted the count rate data for determination of survival half-time [I]. Normal platelet half-time (in 18 normal controls) was 3.7 * 0.04 days (mean f SEM) or 3.7 f 0.4 days (mean f 2.6 SD), giving a normal range of 3.3 to 4.2 days.
Results Three patients died within 30 days of operation, a 3.5y0 early mortality rate (Table). During 5 years of follow-up 5 other patients died, making the 34
THE ANNALS OF THORACIC SURGERY
Throinboembolism after Beall Mitral Valve Replacement REPRESENTATIVE RESULTS AFTER MITRAL VALVE REPLACEMENT
Early Late Mortality Mortality Authors Isom et al. [9] Bonchek et al. [5] Winter et al. [25] Levine et al. [12] Beall et al. [4] Rossi et al. [16] Salomon et al. Lepley et al. [ l l ] Cooley et al. [6] S-E = Starr-Edwards.
E
-
80
-
70
.
60 50
YY
k
40
Valve S-E 6300/ 10/20 S-E 6310120 S-E 6300 S-E 6000 Beall Beall Beall Bj iirk-Shiley Cooley-Cutter
(%)
(%)
8.7 2.0 7.5 17.0 9.5 12.0 3.5 2.6 0
10.9 10.0 12.5 12.7 14.0 14.0 1.4 0
-
.
.
. 20 . 10 . 30
n.
Embolimi (%) 3.2 6.0 15.0 49.0 4.5 8.4 5.2 5.4 0
SALOMON, STEELE, AND PATON
*
N=6
-
1
TE
NO TE
FZG. 2. Platelet survival time following Beall mitral valve replacement in 6 patients with and I I patients without thrombocrnbolisrn (TE) postoperatively.
Only 4 patients (5.2%) were thought to have had late thromboemboli, and in 2 of these the episodes were transitory and of doubtful nature. One patient had to be reoperated upon 4% years after operation because of the appearance of clinical evidence of valve dysfunction. A transitory and variable systolic murmur appeared concomitant with episodic dyspnea. At operation she was found to have a fibrous ingrowth encroaching upon the valve orifice and surrounding the struts. After the second operation her platelet survival time was calculated and was found to be shortened to 2% days, thus putting her into a high-risk category with regard to thromboemboli. She has since been receiving 800 mg per day of sulfinpyrazone. In a separate study, platelet survival times were measured in 17 patients. Nine of these patients were from the operative group, and 8 had been operated on elsewhere and referred for platelet studies. Six patients had a history of thromboembolism, but 11 gave no such history. Of the patients with thromboembolism, 2 were from our operative group and 4 from the referred group. Two of the latter had emboli before valve replacement, and 1 had emboli both before and after replacement. T h e 6 patients with emboli all had shortened platelet survival times with an average of 2.8 f 0.11 days (normal > 3.3 days). Average platelet survival times in patients without emboli was 3.4* 0.13 days, which was within the normal range and was significantly greater ( p < 0.01) than in the group with thromboembolism (Fig. 2). A reduction in platelet survival time, therefore, was found only in those patients with a history of thromboembolism. None of these patients, either with or without emboli, had been treated with platelet-affecting drugs before the studies.
Comment An 897, 5-year survival for isolated Beall mitral valve replacement was obtained in the present series of 76 patients. The 11% combination of early and late mortality rates compares with Beall's late mortality 96
THE ANNALS OF THORACIC SURGERY
Thromboembolism after Beall Mitrnl Valve Refilacement
of 13y0 in the only other large reported series of mitral valve replacements with the Beall valve [2, 41. Late mortality in several other reported series of mitral valve replacements is shown for comparison in the Table. As noted previously, an early perioperative mortality of 3.5y0 was obtained, and comparative figures from other centers are given in the Table. T h e 3 perioperative deaths and the 3 of 5 late deaths for which the cause was known were not associated with thromboembolism, either clinically or upon postmortem examination. T h e cause of late death in 2 patients was not known. In general it was extremely difficult to ascertain the extent and adequacy of the anticoagulation regimen for the postoperative population, and no firm conclusions could be reached in this regard. Well-controlled long-term follow-up studies matching groups who were or were not given anticoagulants are lacking. T h e total incidence of proved or suspected thromboembolic episodes in this series was 5.2y0, which compares favorably with results in other series in which a variety of mitral valve prostheses were used (see the Table). Javier and associates [lo] reported embolization to be four times more frequent among patients not receiving anticoagulants than among those receiving adequate warfarin therapy who were followed up to 19 months. However, Beall [4] does not believe that anticoagulation with antiprothrombin drugs alters the incidence of thromboembolism, and he does not give anticoagulants to his patients. T h e efficacy of these drugs therefore remains in doubt in the prevention of postoperative thromboembolism. Greater reductions in thromboembolism rates during the past few years have been achieved by changes in valve design than by the assiduous use of warfarin. Why should one valve design to better than another? Is it because the pseudointima over a cloth-covered valve is anchored by growth into the interstices of the cloth? Or is it because some surfaces present a less thrombogenic interface to the blood than others? Recent evidence [22] indicates a correlation between platelet survival time, the incidence of thromboembolism, and the type of valve. Patients with valve disease who suffer embolic episodes have been found to have significantly shorter platelet survival times than normal, whether or not they have a prosthesis. A shortened platelet survival time has been found in patients with mitral stenosis without a prosthetic valve but with a history of thromboembolism [23]. Platelet function plays an important role in arterial thrombosis, and the finding of shortened platelet survival in some patients with an intraarterial prosthesis and thromboembolism is consistent with other knowledge of arterial thrombosis. Platelet aggregation and adhesiveness are unchanged in patients with prosthetic valves with or without thromboembolism [22]. Coumadin anticoagulants do not affect platelet function. And if platelet dysfunction is of prime importance in the pathogenesis of embolism arising from prosthetic valves, it would not be surprising that the incidence of
SALOMON, STEELE, AND PATON embolism has not been consistently reduced by the administration of these drugs. Patients with homografts or Beall valves have almost normal platelet survival times. T h e presence of a Model 6100 Starr-Edwards valve results in a significant decrease in platelet survival time, and the reported incidence of thromboembolism in patients with this valve is greater than in those with a homograft or Beall valve. A precise correlation between an abnormal platelet survival time and an increased tendency to thromboembolism could lead to the development of a logical approach to the use of antithrombogenic drugs after operation. First, it would seem advisable to use only those prosthetic valves which have low thrombogenicity, as reflected in the changes they induce in platelet survival times. Second, if a patient has a normal platelet survival time postoperatively, there may be no need to administer antithrombogenic drugs, either warfarin or antiplatelet agents. If, however, a patient is found to have a reduction in platelet survival time, antiplatelet drugs such as sulfinpyrazone or dipyrimadole should be given. Administration of these drugs can prolong platelet survival time [7, 8, 211, and dipyrimadole has been shown to reduce thromboembolism in patients with mitral prosthetic valves [17, 181. T h e remaining link in this chain of logic, yet to be demonstrated, is to show that correction of abnormal platelet survival time to normal eliminates or reduces the chance of thromboembolism. T h e results in this series confirm previous findings that the incidence of thromboembolism is low with the Beall valve and that this low incidence is associated with only a minimal aberration from normal of platelet survival time.
References I . Aster, R. H., and Iandl, J. H. J Clin Invest 43~843,1964.
Platelet sequestration in man: I. Methods.
2. Beall, A. C., Jr., Bloodwell, R. D., Arbegast, N. R., Liotta, D., Cooley, D. A., and DeBakey, M. E. Mitral Valve Replacement with Dacron-covered Disc Prosthesis to Prevent Thromboembolism: Clinical Experience with 202 Cases. In L. A. Brewer, 111 (Ed), Prosthetic Heart Valves. Springfield, Ill.: Thomas, 1969. Chap 21, p 319. 3. Beall, A. C., Jr., Bloodwell, R. D., Liotta, D., Cooley, D. A., and DeBakey, M. E. Clinical experience with a Dacron velour-covered Teflon-disc mitralvalve prosthesis. Ann. Thorac Surg 5:402, 1968. 4. Beall, A. C., Jr., Morris, G. C., Jr., Noon, G. P., Guinn, G. A., Reul, G. J., Jr., Lefrak, E. A., and Greenberg, S. D. An improved mitral valve prosthesis. A n n Thorac Surg 15:25, 1973. 5. Bonchek, L. I., Anderson, R. P., and Starr, A. Mitral valve replacement with cloth-covered composite-seat prostheses. J Thorac Cardiouasc Surg 67:93, 1974. 6. Cooley, D. A., Okies, J. E., Wukasch, D. C., Sandiford, F. M., and Hallman, G. L. Ten-year experience with cardiac valve replacement: Results with a new mitral prosthesis. A n n Surg 177:818, 1973. 7. Harker, L. A., and Slichter, S. T. Studies of platelet and fibrinogen kinetics in patients with prosthetic heart valves. N Engl J M e d 283: 1302, 1970.
38
THE ANNALS OF THORACIC SURGERY
Thromboembolism after Beall Mitral Valve Replacement 8. Harker, L. A., and Slichter, S. T. Platelet and fibrinogen consumption in man. N Engl J Med 287:999, 1972. 9. Isom, 0. W., Williams, C. D., Falk, E. A., Glassman, E., and Spencer, F. C. Long term evaluation of cloth covered metallic ball prostheses. J Thorac Cardiovasc Surg 64:354, 1972. 10. Javier, R. P., Hildner, F. J., Berry, W., Greenberg, J. J., and Samet, P. Systemic embolism and the Beall mitral valve prosthesis. Ann Thorac Surg 10:20, 1970. 11. Lepley, D., Reuben, C. F., Flemma, R. ,I., Huston, J. H., Manley, I., Hoffman, J., and Tector, A. J. Experience with the Bjiirk-Shiley valve. Circulation 48 (Suppl 111):51, 1973. 12. Levine, F. H., Copeland, J . G., and Morrow, A. G. Prosthetic replacement of the mitral valve: Continuing assessment of the 100 patients operated upon during 1961-65. Circulation 47:518, 1973. 13. Linhart, J. W., Barold, S. S., Hildner, F. J., Samet, P., Piccinini, J. c., Marsten, J . L., and Greenberg, J. J. Clinical and hernodynamic findings following replacement of the mitral valve with a Beall valve prosthesis. Circulation 39 (Suppl I): 127, 1969. 14. Ramsey, H. W., Williams, J. C., Jr., Vernon, C. R., Wheat, M. W., Daicoff, G. R., and Bartley, T . D. Hernodynamic findings following replacement of the mitral valve with the Beall valve prosthesis. J Thorac Cardiovasc Surg 62:624, 1971. 15. Reid, J . A., Stevens, T . W., Sigwart, U., Fulweber, R. C., and Alexander, J. K. Hemodynamic evaluation of the Beall mitral valve prosthesis. Circulation 45 (Suppl I):l, 1972. 16. Rossi, N. P., Kongtahworn, C., and Ehrenhaft, J . L. Single valve replacement with the Beall mitral prosthesis. J Thorac Cwdiovasc Surg 67:83, 1974. 17. Sullivan, J. M., Harken, D. E., and Gorlin, R. Pharmacologic control of thromboembolic complications of cardiac valve replacement: Preliminary report. N Engl J Med 279:576, 1968. 18. Sullivan, J. M., Harken, D. E., and Gorlin, R. Pharmacologic control of thromboembolic complications of cardiac valve replacement. N Engl J Med 284:1391, 1971. 19. Vogel, 1. H. K., Paton, B. C., Overy, H., Pappas, G., Davies, D. H., and Blount, S. G., Jr. Advantages of Beall valve prosthesis. Chest 49:249, 1971. 20. Vogel, J. H. K., Paton, B. C., Overy, H. R., Pappas, G., Davies, D. H., and Blount, S. G., Jr. Long-term Results following Mitral Valve Replacement with Disc Valves. I n J. H. K. Vogel (Ed), Advances in Cardiology. Basel: Karger, 1972. Vol 7, p 65. 21. Weily, H. S., and Genton, E. Altered platelet function in patients with prosthetic mitral valves: Effects of sulfinpyrazone therapy. Circulation 42:967, 1970. 22. Weily, H. S., Steele, P. P., Davies, D. H., Pappas, G., and Genton, E. Platelet function studies in patients with substitute heart valves. Circulation 43, 44 (Suppl II):68, 1971. 23. Weily, H. S., Steele, P. P., Davies, D. H., Pappas, G., and Genton, E. Thromboembolism i n rheumatic heart disease: Correlation with platelet function studies. Circulation 45, 46 (Suppl 11): 107, 1972. 24. Weily, H. S., Steele, P. P., and Genton, E. Platelet survival in patients with a Beall valve: Relation to low incidence of thromboembolism. A m J Cardiol 30:229, 1972. 25. Winter, T. Q., Reis, R. L., Glanc , D. L., Roberts, W. C., Epstein, S. E., and Morrow, A. G. Current status o l t h e Starr-Edwards cloth covered prosthetic cardiac valves. Circulation 45 (Suppl I):14, 1972.
VOL. 19,
NO. 1, JANUARY,
1975
39
I
n 1967 Beall [Z, 31 introduced a Dacron velour-covered Teflon-disc mitral valve prosthesis which several recent studies [4, 10, 161 have shown to be comparable, if not superior, to other existing mitral valve designs in terms of early and late mortality and low incidence of thromboembolization. Beall reported a 4.5% total incidence of thromboembolic episodes with only a 3.6% incidence of late emboli [4]. Previous studies have described hemodynamic results after Beall valve replacement associated with symptomatic and functional postoperative improvement [13-1 5, 201. Nevertheless, symptomatic improvement is often accompanied by persistent postoperative transvalvular pressure gradients and elevated mean pulmonary artery and pulmonary artery wedge pressures, all of which significantly increase during exercise [ 15, 191. T h e present study is concerned with late mortality and morbidity in a consecutive series of 76 patients who survived isolated mitral valve replacement with a Beall valve prosthesis. T h e efficacy of and need for anticoagulation continues to be a matter for discussion. Beall [4] has found that there is little or no difference in the incidence of emboli between patients receiving anticoagulants and those not receiving them. Others have come to the same conclusion with difl'erent types of valves, which suggests that whatever factors are involved are not seriously influenced by warfarin anticoagulation. Weily, Steele, and Genton [24] studied platelet survival times in 9 patients with Beall valves and found the platelet survival times to be almost normal. Similar findings in patients with other types of valves were From the Departments of Medicine and Surgery, University of Colorado Medical Center, Denver, Colo. Accepted for publication Aug. 8, 1974. Address reprint requests to Dr. Paton, Department of Surgery, University of Colorado Medical Center, 4200 E. Ninth Ave., Denver, Colo. 80220. VOL.
19, NO.
1, JANUARY,
1975
33
SALOMON, STEELE, AND PATON
associated with a low incidence of thromboembolism [22]. Prognostic and therapeutic implications of these findings are discussed in this paper.
Clinical Material and Methods Between August 29, 1967, and March 28, 1973 (5 years 7 months), 76 mitral valves were replaced by Beall valves in patients with isolated mitral disease at the University of Colorado Medical Center and the Denver Veterans Administration Hospital. Only patients undergoing isolated mitral valve replacement are included in this study; 28 additional patients operated upon during the same period for either double-valve replacement or valve replacement combined with coronary artery bypass grafting were excluded. All patients were considered to be in N.Y.H.A. Class 111 or IV preoperatively, and no patients were denied operation because of terminal cardiac dysfunction. A total of 50 small (including 4 pediatric), 19 medium, and 7 large Beall valves were inserted. There were 48 female and 28 male patients ranging from 10 through 63 years with a mean age of 47. Standard cardiopulmonary bypass procedures were employed, using disposable Travenol oxygenators primed with lactated Ringer’s solution. Throughout the 5S-year period 20 patients have been lost to follow-up at various intervals postoperatively and have been considered only for as long as appropriate follow-up contact was made. Many patients were not local residents but came from several neighboring states; hence only indirect contact through their local referring physician could be made. Accurate evaluation of which patients were adequately maintained on oral anticoagulants was difficult to obtain. In a separate study, platelet survival times were determined in 17 patients (12 men, 5 women), all of whom had a Teflon disc valve. None had a valve with a pyrolytic carbon disc. Nine of these patients are included in the operative follow-up series, and 8 of the 17 were referred specifically for platelet studies. Six of the 17 patients (including 2 from the operative series) examined for platelet survival times suffered strokes. T h e remaining 11 patients had no evidence of thromboembolism. Platelet survival time was measured by labeling autologous platelets obtained from 450 ml of blood with 100 to 150 pCi of chromium 51 [l]. T h e labeled platelets were reinfused and samples obtained 2 to 3 hours later and then daily for 7 days. T h e platelet button was counted, and a single exponent fitted the count rate data for determination of survival half-time [I]. Normal platelet half-time (in 18 normal controls) was 3.7 * 0.04 days (mean f SEM) or 3.7 f 0.4 days (mean f 2.6 SD), giving a normal range of 3.3 to 4.2 days.
Results Three patients died within 30 days of operation, a 3.5y0 early mortality rate (Table). During 5 years of follow-up 5 other patients died, making the 34
THE ANNALS OF THORACIC SURGERY
Throinboembolism after Beall Mitral Valve Replacement REPRESENTATIVE RESULTS AFTER MITRAL VALVE REPLACEMENT
Early Late Mortality Mortality Authors Isom et al. [9] Bonchek et al. [5] Winter et al. [25] Levine et al. [12] Beall et al. [4] Rossi et al. [16] Salomon et al. Lepley et al. [ l l ] Cooley et al. [6] S-E = Starr-Edwards.
E
-
80
-
70
.
60 50
YY
k
40
Valve S-E 6300/ 10/20 S-E 6310120 S-E 6300 S-E 6000 Beall Beall Beall Bj iirk-Shiley Cooley-Cutter
(%)
(%)
8.7 2.0 7.5 17.0 9.5 12.0 3.5 2.6 0
10.9 10.0 12.5 12.7 14.0 14.0 1.4 0
-
.
.
. 20 . 10 . 30
n.
Embolimi (%) 3.2 6.0 15.0 49.0 4.5 8.4 5.2 5.4 0
SALOMON, STEELE, AND PATON
*
N=6
-
1
TE
NO TE
FZG. 2. Platelet survival time following Beall mitral valve replacement in 6 patients with and I I patients without thrombocrnbolisrn (TE) postoperatively.
Only 4 patients (5.2%) were thought to have had late thromboemboli, and in 2 of these the episodes were transitory and of doubtful nature. One patient had to be reoperated upon 4% years after operation because of the appearance of clinical evidence of valve dysfunction. A transitory and variable systolic murmur appeared concomitant with episodic dyspnea. At operation she was found to have a fibrous ingrowth encroaching upon the valve orifice and surrounding the struts. After the second operation her platelet survival time was calculated and was found to be shortened to 2% days, thus putting her into a high-risk category with regard to thromboemboli. She has since been receiving 800 mg per day of sulfinpyrazone. In a separate study, platelet survival times were measured in 17 patients. Nine of these patients were from the operative group, and 8 had been operated on elsewhere and referred for platelet studies. Six patients had a history of thromboembolism, but 11 gave no such history. Of the patients with thromboembolism, 2 were from our operative group and 4 from the referred group. Two of the latter had emboli before valve replacement, and 1 had emboli both before and after replacement. T h e 6 patients with emboli all had shortened platelet survival times with an average of 2.8 f 0.11 days (normal > 3.3 days). Average platelet survival times in patients without emboli was 3.4* 0.13 days, which was within the normal range and was significantly greater ( p < 0.01) than in the group with thromboembolism (Fig. 2). A reduction in platelet survival time, therefore, was found only in those patients with a history of thromboembolism. None of these patients, either with or without emboli, had been treated with platelet-affecting drugs before the studies.
Comment An 897, 5-year survival for isolated Beall mitral valve replacement was obtained in the present series of 76 patients. The 11% combination of early and late mortality rates compares with Beall's late mortality 96
THE ANNALS OF THORACIC SURGERY
Thromboembolism after Beall Mitrnl Valve Refilacement
of 13y0 in the only other large reported series of mitral valve replacements with the Beall valve [2, 41. Late mortality in several other reported series of mitral valve replacements is shown for comparison in the Table. As noted previously, an early perioperative mortality of 3.5y0 was obtained, and comparative figures from other centers are given in the Table. T h e 3 perioperative deaths and the 3 of 5 late deaths for which the cause was known were not associated with thromboembolism, either clinically or upon postmortem examination. T h e cause of late death in 2 patients was not known. In general it was extremely difficult to ascertain the extent and adequacy of the anticoagulation regimen for the postoperative population, and no firm conclusions could be reached in this regard. Well-controlled long-term follow-up studies matching groups who were or were not given anticoagulants are lacking. T h e total incidence of proved or suspected thromboembolic episodes in this series was 5.2y0, which compares favorably with results in other series in which a variety of mitral valve prostheses were used (see the Table). Javier and associates [lo] reported embolization to be four times more frequent among patients not receiving anticoagulants than among those receiving adequate warfarin therapy who were followed up to 19 months. However, Beall [4] does not believe that anticoagulation with antiprothrombin drugs alters the incidence of thromboembolism, and he does not give anticoagulants to his patients. T h e efficacy of these drugs therefore remains in doubt in the prevention of postoperative thromboembolism. Greater reductions in thromboembolism rates during the past few years have been achieved by changes in valve design than by the assiduous use of warfarin. Why should one valve design to better than another? Is it because the pseudointima over a cloth-covered valve is anchored by growth into the interstices of the cloth? Or is it because some surfaces present a less thrombogenic interface to the blood than others? Recent evidence [22] indicates a correlation between platelet survival time, the incidence of thromboembolism, and the type of valve. Patients with valve disease who suffer embolic episodes have been found to have significantly shorter platelet survival times than normal, whether or not they have a prosthesis. A shortened platelet survival time has been found in patients with mitral stenosis without a prosthetic valve but with a history of thromboembolism [23]. Platelet function plays an important role in arterial thrombosis, and the finding of shortened platelet survival in some patients with an intraarterial prosthesis and thromboembolism is consistent with other knowledge of arterial thrombosis. Platelet aggregation and adhesiveness are unchanged in patients with prosthetic valves with or without thromboembolism [22]. Coumadin anticoagulants do not affect platelet function. And if platelet dysfunction is of prime importance in the pathogenesis of embolism arising from prosthetic valves, it would not be surprising that the incidence of
SALOMON, STEELE, AND PATON embolism has not been consistently reduced by the administration of these drugs. Patients with homografts or Beall valves have almost normal platelet survival times. T h e presence of a Model 6100 Starr-Edwards valve results in a significant decrease in platelet survival time, and the reported incidence of thromboembolism in patients with this valve is greater than in those with a homograft or Beall valve. A precise correlation between an abnormal platelet survival time and an increased tendency to thromboembolism could lead to the development of a logical approach to the use of antithrombogenic drugs after operation. First, it would seem advisable to use only those prosthetic valves which have low thrombogenicity, as reflected in the changes they induce in platelet survival times. Second, if a patient has a normal platelet survival time postoperatively, there may be no need to administer antithrombogenic drugs, either warfarin or antiplatelet agents. If, however, a patient is found to have a reduction in platelet survival time, antiplatelet drugs such as sulfinpyrazone or dipyrimadole should be given. Administration of these drugs can prolong platelet survival time [7, 8, 211, and dipyrimadole has been shown to reduce thromboembolism in patients with mitral prosthetic valves [17, 181. T h e remaining link in this chain of logic, yet to be demonstrated, is to show that correction of abnormal platelet survival time to normal eliminates or reduces the chance of thromboembolism. T h e results in this series confirm previous findings that the incidence of thromboembolism is low with the Beall valve and that this low incidence is associated with only a minimal aberration from normal of platelet survival time.
References I . Aster, R. H., and Iandl, J. H. J Clin Invest 43~843,1964.
Platelet sequestration in man: I. Methods.
2. Beall, A. C., Jr., Bloodwell, R. D., Arbegast, N. R., Liotta, D., Cooley, D. A., and DeBakey, M. E. Mitral Valve Replacement with Dacron-covered Disc Prosthesis to Prevent Thromboembolism: Clinical Experience with 202 Cases. In L. A. Brewer, 111 (Ed), Prosthetic Heart Valves. Springfield, Ill.: Thomas, 1969. Chap 21, p 319. 3. Beall, A. C., Jr., Bloodwell, R. D., Liotta, D., Cooley, D. A., and DeBakey, M. E. Clinical experience with a Dacron velour-covered Teflon-disc mitralvalve prosthesis. Ann. Thorac Surg 5:402, 1968. 4. Beall, A. C., Jr., Morris, G. C., Jr., Noon, G. P., Guinn, G. A., Reul, G. J., Jr., Lefrak, E. A., and Greenberg, S. D. An improved mitral valve prosthesis. A n n Thorac Surg 15:25, 1973. 5. Bonchek, L. I., Anderson, R. P., and Starr, A. Mitral valve replacement with cloth-covered composite-seat prostheses. J Thorac Cardiouasc Surg 67:93, 1974. 6. Cooley, D. A., Okies, J. E., Wukasch, D. C., Sandiford, F. M., and Hallman, G. L. Ten-year experience with cardiac valve replacement: Results with a new mitral prosthesis. A n n Surg 177:818, 1973. 7. Harker, L. A., and Slichter, S. T. Studies of platelet and fibrinogen kinetics in patients with prosthetic heart valves. N Engl J M e d 283: 1302, 1970.
38
THE ANNALS OF THORACIC SURGERY
Thromboembolism after Beall Mitral Valve Replacement 8. Harker, L. A., and Slichter, S. T. Platelet and fibrinogen consumption in man. N Engl J Med 287:999, 1972. 9. Isom, 0. W., Williams, C. D., Falk, E. A., Glassman, E., and Spencer, F. C. Long term evaluation of cloth covered metallic ball prostheses. J Thorac Cardiovasc Surg 64:354, 1972. 10. Javier, R. P., Hildner, F. J., Berry, W., Greenberg, J. J., and Samet, P. Systemic embolism and the Beall mitral valve prosthesis. Ann Thorac Surg 10:20, 1970. 11. Lepley, D., Reuben, C. F., Flemma, R. ,I., Huston, J. H., Manley, I., Hoffman, J., and Tector, A. J. Experience with the Bjiirk-Shiley valve. Circulation 48 (Suppl 111):51, 1973. 12. Levine, F. H., Copeland, J . G., and Morrow, A. G. Prosthetic replacement of the mitral valve: Continuing assessment of the 100 patients operated upon during 1961-65. Circulation 47:518, 1973. 13. Linhart, J. W., Barold, S. S., Hildner, F. J., Samet, P., Piccinini, J. c., Marsten, J . L., and Greenberg, J. J. Clinical and hernodynamic findings following replacement of the mitral valve with a Beall valve prosthesis. Circulation 39 (Suppl I): 127, 1969. 14. Ramsey, H. W., Williams, J. C., Jr., Vernon, C. R., Wheat, M. W., Daicoff, G. R., and Bartley, T . D. Hernodynamic findings following replacement of the mitral valve with the Beall valve prosthesis. J Thorac Cardiovasc Surg 62:624, 1971. 15. Reid, J . A., Stevens, T . W., Sigwart, U., Fulweber, R. C., and Alexander, J. K. Hemodynamic evaluation of the Beall mitral valve prosthesis. Circulation 45 (Suppl I):l, 1972. 16. Rossi, N. P., Kongtahworn, C., and Ehrenhaft, J . L. Single valve replacement with the Beall mitral prosthesis. J Thorac Cwdiovasc Surg 67:83, 1974. 17. Sullivan, J. M., Harken, D. E., and Gorlin, R. Pharmacologic control of thromboembolic complications of cardiac valve replacement: Preliminary report. N Engl J Med 279:576, 1968. 18. Sullivan, J. M., Harken, D. E., and Gorlin, R. Pharmacologic control of thromboembolic complications of cardiac valve replacement. N Engl J Med 284:1391, 1971. 19. Vogel, 1. H. K., Paton, B. C., Overy, H., Pappas, G., Davies, D. H., and Blount, S. G., Jr. Advantages of Beall valve prosthesis. Chest 49:249, 1971. 20. Vogel, J. H. K., Paton, B. C., Overy, H. R., Pappas, G., Davies, D. H., and Blount, S. G., Jr. Long-term Results following Mitral Valve Replacement with Disc Valves. I n J. H. K. Vogel (Ed), Advances in Cardiology. Basel: Karger, 1972. Vol 7, p 65. 21. Weily, H. S., and Genton, E. Altered platelet function in patients with prosthetic mitral valves: Effects of sulfinpyrazone therapy. Circulation 42:967, 1970. 22. Weily, H. S., Steele, P. P., Davies, D. H., Pappas, G., and Genton, E. Platelet function studies in patients with substitute heart valves. Circulation 43, 44 (Suppl II):68, 1971. 23. Weily, H. S., Steele, P. P., Davies, D. H., Pappas, G., and Genton, E. Thromboembolism i n rheumatic heart disease: Correlation with platelet function studies. Circulation 45, 46 (Suppl 11): 107, 1972. 24. Weily, H. S., Steele, P. P., and Genton, E. Platelet survival in patients with a Beall valve: Relation to low incidence of thromboembolism. A m J Cardiol 30:229, 1972. 25. Winter, T. Q., Reis, R. L., Glanc , D. L., Roberts, W. C., Epstein, S. E., and Morrow, A. G. Current status o l t h e Starr-Edwards cloth covered prosthetic cardiac valves. Circulation 45 (Suppl I):14, 1972.
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