- Email: [email protected]
Late causes of death after mitral valve replacement
Late causes of death after mitral valve replacement Analysis 0/ 36 cases Alfred Ioassin, M.D., * and Jesse E. Edwards, M.D., Minneapolis and St. Paul, Minn.
Ithen causes an earlier communication, we' described of death among 93 patients who died less than 30 days after replacement of the mitral valve for various types of mitral valve disease. This communication concerns itself with 36 cases of mitral valve replacement in which the patients survived for at least 30 days after the operation. Eleven of the patients survived between 2 and 6 years following the operation. Materials and methods Thirty-six patients, in each of whom the mitral valve alone was replaced by a prosthesis and in whom death occurred 30 days or more from the time of operation, were reviewed. All cases obtained during a period from 1961 through 1972 which met the above-mentioned criteria were included, the principal sources being the University of Minnesota Hospitals and the United Hospitals, Inc.-Miller Division (formerly the From the Departments of Pathology. United Hospitals, Inc. -Miller Division, St. Paul, Minn. 55102, and University of Minnesota, Minneapolis, Minn. 55455. This study was supported by Public Health Service Research Grant 5 ROI HL05694 and Research Training Grant 5 TOI HL05570 from the National Heart and Lung Institute. Received for publication July 17, 1972. ·Supported by a grant from Conseil de la Recherche Medicale du Quebec, Quebec, Canada.
Charles T. Miller Hospital). Fewer cases were obtained from other institutions. All cases from which specimens were received and which fulfilled the criteria mentioned were included. The patients ranged in age from 24 to 72 years and included 21 male and 17 female subjects. The types of mitral valve disease for which the natural valve was replaced by a prosthesis included stenosis of rheumatic nature and mitral insufficiency of various etiologic types; only 1 patient required valve replacement as the result of myocardial infarction. In 7 of the patients with mitral stenosis, a mitral commissurotomy had been done at varying times prior to replacement of the valve. The prostheses varied in design, but in most cases the Starr-Edwards Model 6120, which has a movable ball, was used. In each case, the specimen of heart obtained at autopsy was available and reviewed. In certain cases, more than one pathologic abnormality was observed. These were considered along with the abstract of the clinical features so that one cause of death was named per patient. The causes of death could be grouped into four categories as follows: (1) residual effect or complication of operation, (2) associated disease, ( 3) complication of 255
The Journal of
256
Joassin and Edwards
Thoracic and Cardiovascular Surgery
Table I. Summary of data in 36 cases studied Corollary atherosclerosis Postoperative interval (mo.)
Cause of death
No. of cases
Residual effect or complication of operation
11
11
9 3
9 3 1 5 1
Cardiac Myocardial failure Left ventricular outflow obstruction Dehiscence Cerebral Hepatic Associated disease Cardiomyopathy Coronary atherosclerosis Complication of prosthesis Thrombosis with stenosis Thrombosis with embolism Bacterial endocarditis Noncardiac disease Total
prosthesis, and (4 ) non-cardiac disease. These categories are defined below. The category of residual effect or complication of operation included those conditions, such as persistent myocardial failure following operation, malposition of prosthesis causing left ventricular outflow obstruction, dehiscence of the seat of the prosthesis, and those conditions secondarily related to the operation, such as cerebral anoxia and hepatitis. Associated disease included those conditions present prior to the operation which were of such significance as to be considered the basis for death. Complications of prothesis included (1) thrombosis in relation to the prosthesis, serving either to make the prosthesis stenotic or to be a basis for systemic arterial embolism, and (2) bacterial endocarditis in relation to the prosthesis. Observations
Among the 36 cases studied, the causes of death were distributed as follows: residual effect or complication of operation, 11 cases (30 per cent); associated disease, 7
1-7
I
8-23
o
I
24-72
o
o
o o
1
o o o
o o o
7 2 5
2
2
3
13 5 4
4 1 I 2
5
2
36
19
1
5 1 1
4
o
2
o o
o
o
2
Grade 21 Grade 3 or less or more 10 8 3 1 4 1 1
2 2
I
o
3
6
11
1 1 1
3 2 I
5 3 3
2
4
11
27
2
6
1 1
o o 1
o
o 5
o 5
2
o I I
9
cases (20 per cent); complication of prosthesis, 13 cases (36 per cent); and noncardiac diseases, 5 cases (14 per cent). Table I lists the causes of death, the interval of postoperative survival, and the grade of coronary atherosclerosis. Among the 36 patients, death occurred between the first and seventh postoperative months in 19 cases, between 8 months and 2 years in 6 cases, and between 2 and 6 years in II cases. Among the latter, 4 patients lived into the sixth postoperative year. The causes of death of the 19 patients who died between 1 and 7 months after operation were distributed fairly uniformly among the several categories of causes of death while, among the group with longest survival times, the common cause of death was a complication of the prosthesis. Residual effect or complication of operation. In each of the 11 patients in whom the cause of death was a residual effect or complication of the operation, death occurred less than 7 months after the operation. This group was subdivided according to the site of residual effect or complication of operation as follows: ( I) cardiac, 9
Volume 65 Number 2
Death after mitral valve replacement
257
February , 1973
cases; (2) cerebral, 1 case; and (3) hepatic, I case. In nine of the cases in which death was attributed to a residual effect or complication of the operation, a cardiac condition was present such as myocardial failure (3 cases), left ventricular outflow obstruction (I case), and dehiscence of the seat of the mitral prosthesis in the absence of bacterial endocarditis (5 cases). Each of the 3 patients with myocardial failure had cardiac hypertrophy, the hearts weighing 630, 700, and 700 grams, respectively. One manifested a low cardiac output after operation. He remained in a state of intractable cardiac failure in spite of vigorous medical treatment and died 6 weeks after operation. The second patient exhibited a stormy postoperative course from which he recovered. Sudden death occurred 5 months postoperatively. At autopsy, the heart, except for being greatly hypertrophied, manifested no unusual features. The coronary arteries were devoid of significant degrees of atherosclerosis. The third patient had shown severe pulmonary hypertension preoperatively (120/ 16 mrn, Hg). After experiencing a continuous state of congestive cardiac failure postoperatively, the patient died 4 months after replacement of the mitral valve. Left ventricular outflow obstruction by the mitral prosthesis was considered the cause of death in I patient. This patient, whose primary condition had been mitral stenosis, died 7 weeks postoperatively. In the absence of bacterial endocarditis, dehiscence of the prosthesis at the lateral aspect of the mitral ring was observed in 5 cases (Fig. I). In each of these cases, mitral insufficiency was the basis for the clinical picture of postoperative heart failure and pulmonary edema . Death occurred 2 months postoperatively in 3 cases and at 6 months and 7 months, respectively, in the other 2. Cerebral disease was the cause of death in I patient. This patient had developed cardiac arrest soon after completion of the operation; although cardiac resuscitation
Fig. 1. Mitral valve prosthesis from above. There is a dehiscence (between arrows) of the valvular prosthesis from the mitral valve ring in the lateral aspect of the valve area. Death resulted from mitral insufficiency and congestive heart failure 2 months after insertion of the prosthet ic valve.
had been accomplished, a cerebral deficit resulted and death occurred 17 weeks postoperatively. Hepatitis was considered to be the cause of death in I case. This complication appeared 4 months after the operation and resulted in death of the patient 2 weeks after onset. Associated disease. Of the 7 patients in whom death appeared to have resulted from diseases associated with the mitral valve disease, the associated diseases were subdivided into two groups: ( 1) cardiomyopathy and (2) coronary atherosclerosis. Cardiomyopathy had been the basis for mitral insufficiency in 2 patients who had undergone mitral valve replacement. The first of these patients died suddenly 3 years postoperatively, while the second developed congestive heart failure I year after operation. He was supported by medical treatment but died 3 years and 8 months postoperatively . In both patients, the myocardium had numerous scars attributed to antecedent myocarditis (Fig. 2). In each of the 36 cases of this study, coronary atherosclerosis as seen in the
The Journal of
25 8
Ioassin and Edwards
Thoracic and Cardiovascular Surgery
PII. 1. Myocarditis. Interior of left ventricle 3 years and 8 months after replacement of the mitral valve for mitral insufficiency associated with chronic myocarditis. Endocardial fibroelastosis is a prominent feature. Death was attributed to the associated changes of antecedent myocarditis.
pathologic specimen was graded as 2 or less or else 3 or more. Grade 2 represented . up to 50 per cent narrowing of the lumen, while Grade 3 signified more than 50 per cent narrowing of the lumen. It is apparent from Table I that, of the 36 patients in this study, 27 had Grade 2 or less coronary atherosclerosis while 9 patients (22 per cent) had coronary atherosclerosis Grade 3 or more. In 4 of the 9 with Grade 3 coronary atherosclerosis, this condition did not appear to contribute to death, while in the remaining 5 patients it was considered to have caused death . Common phenomenon among 5 patients in whom death was attributed to coronary disease was sudden unexpected death . Pathologically, myocardial scarring from earlier myocardial infarction but without evidence of acute ischemic necrosis of myocardial tissue was a characteristic. In 1 of the 5 patients dying of coronary disease, mitral insufficiency resulting from myocardial infarction had been the indication for mitral valve replacement. In another case, in addition to mitral valve replacement for mitral stenosis, a saphenous vein graft was inserted in the coronary arterial system 42
months prior to death . The survival time after operation in the 5 patients whose deaths were attributed to coronary disease was 7 months in 2 patients, between 17 and 20 months in 2, and 42 months in the fifth. Complication of prosthesis. In 13 patients, death was attributed to a complication of the prosthesis. In 9 this took the form of thrombosis, and in 4 death was caused by bacterial endocarditis. Thrombosis. Although superficial thrombosis on or in relation to the seat of the prosthetic valve was commonly found among the entire series of patients, there were 9 cases in which thrombosis represented a major complication and cause of death. In 5 of these, thrombosis was extensive and accounted for obstruction to the inlet of the prosthesis and/or restriction in motion of the ball (Fig. 3) . Congestive heart failure was present in each. Among patients in this group, death occurred Ph, 17, 36, 48, and 60 months after operation. In 4 other cases, thrombosis was the source of major systemic arterial embolism 18, 29, (Fig. 4) , and death occurred 1~, and 60 months after operation. In each case, autopsy revealed thrombi deposited along the atrial and ventricular aspects of the prosthesis. In 3 cases, extensive left atrial mural thrombosis was present as wen. In I of the patients with systemic arterial embolism in additionto thrombi in relation to the prosthesis, a false aneurysm was present in the base of the left ventricle (Fig. 5). This lesion may have been a source of cerebral embolism. Its mouth lay just inferior to the seat of the prosthesis. It is assumed that the basis for the aneurysm was laceration of the left ventricular wall at the time of operation 5 years previously. Bacterial endocarditis. Bacterial endocarditis (Figs. 6 and 7) in relation to the mitral prosthesis was observed in 4 cases, in each of which death was caused by systemic embolism. In 2 of the 4 patients with bacterial endocarditis, an infectious complication or a procedure could be identified as a probable cause of infection. One patient had developed empyema in
Volume 65 Number 2 Februory, 1973
Death after mitral valve replacement
259
FfI. 3. Thrombosis of mitral valve prosthesis 3 years postoperatively. a, Mitral valve prosthesis
viewed from above. The seat of the valve is obscured by thrombotic material which partially encroaches upon the inlet to the valve. b, View from left ventricular aspect shows thrombotic material along the struts and within the cage, thereby restricting motion of the ball.
.!lo.-.
Fig. 4. Photomicrograph of anterior descending coronary artery. Occlusion of lumen by embolus of thrombus upon mitral valve prosthesis . (Hematoxylin and eosin; original magnification x23.)
the early postoperative period and died IIh months after operation, Autopsy revealed gram-positive cocci in the empyema exudate as well as in vegetations near the mitral prosthesis. Multiple emboli to the myocardium were associated with foci of acute myocardial infarction. In another case of bacterial endocarditis,
FIg. 5. Lateral view of left atrium (L.A.) and left ventricle (L.V.) in a patient with mitral valve re-
placement 5 years previously. Thrombotic material is present on the atrial surface of the seat of the valve and along the inlet to the valve. (The ball has been removed from the prosthesis.) At the base of the left ventricle is a false aneurysm (F.A.) which appears to have resulted from laceration of the left ventricle at the time of operation. Thrombotic material in the aneurysm and at the seat of the valve was a potential source for systemic embolism, which was the cause of death.
The Journol of
260
Joassin and Edwards
Thoracic and Cardiovascular Surgery
Fig. 6. Bacterial endocarditis complicating mitral valve replacement. Operation 3 months previously. a, The mitral prosthesis viewed from above. Thrombotic material is present along the atrial aspect of the seat. Probe shows the site of dehiscence of the prosthesis from the mitral ring. b, The mitral valve prosthesis viewed from the left ventricular aspect. Medial to the seat of the valve is a vegetation (between arrows) extending into the ventricular septum and representing a site of invasive bacterial endocarditis. There is a secondary site of infection in the subaortic area (single arrow).
a urethral stricture was noted to be present after the mitral valve replacement. Penicillin was administered prophylactically with each of several therapeutic urethral dilatations. Clinical signs of bacterial endocarditis became apparent several days before death, 38 months after replacement of the mitral valve. At autopsy, both the atrial and ventricular aspects of a disctype prosthesis were found to be covered by thrombi, and adjacent tissue showed signs of bacterial infection (Fig. 7). An additional finding in this case was external compression of the left circumflex artery by suture material used to secure the mitral prosthesis, as described by others.v 3 The related, healed posterobasal infarct of the left ventricle which we found did not appear to have contributed to the death of the patient. Of the 2 remaining patients with bacterial endocarditis, 1 died of embolism to the right coronary artery 11 months after operation. The last patient died 3 months postoperatively of cerebral embolism. Partial dehiscence of the base of the prosthesis was present in this case (Fig. 6). Noncardiac diseases. Five patients were
considered to have died of noncardiac causes. The relationship is questionable in 1, as the patient died of pulmonary embolism 5 years after the operation. Among the remaining 4 patients, 1 died from rupture of a congenital arteriovenous fistula of the brain 2 months postoperatively. One subject committed suicide 6 months after the operation. The third patient died 15 months postoperatively from undifferentiated pulmonary carcinoma, and the last died of Hodgkin's disease 72 months postoperatively. Comment In this study on deaths occurring between 1 month and 6 years after replacement of the mitral valve, the causes of death related to the cardiac disease could be placed into three categories as follows: ( 1) residual effect or complication of the operation, (2) associated disease, and (3) complication of the prosthesis. In general, our observations conform with those of other studies':" on late effects of valve replacement. Death occurring 7 months or more after operation resulted from the various types of death, while all of the deaths
Volume 65 Number 2
Death after mitral valve replacement
261
February. 1973
Fig. 7. Bacterial endocarditis in a case in which a urethral stricture was dilated following mitral valve replacement. Death resulted 38 months after replacement of mitral valve by disctype prosthesis. a. Mitral valve prosthesis viewed from above. The latter is obscured by thrombotic material present over its inlet. Discoloration of the adjacent left atrial wall is a feature of extension of bacterial infection. b, Left ventricle and the mitral valve prosthesis viewed from below. Vegetative material of bacterial endocarditis is deposited along the ventricular aspect of the base of the prosthesis, and similar material extends along the struts of the prosthesis.
resulting from a residual effect or complication of the operation occurred from 1 to 7 months after operation. Among the 11 patients dying of a residual effect or complication of the operation, 3 had marked cardiomegaly, a condition in itself which may have disturbing prognostic significance.w
The incidence of significant coronary atherosclerosis (Grade 3) was 22 per cent in this series of patients who survived at least 1 month following operation. The incidence of coronary deaths in our series was about the same as in the study of Starr." A higher figure of 33 per cent incidence of coronary atherosclerosis Grade 3 or more was observed in our- earlier study involving patients who failed to live longer than 1 month after mitral valve replacement. The difference may be an indication of the greater hazard of the procedure to the sub-
ject with significant atherosclerosis than to the patient with lesser degrees of this condition. Among the 9 patients with coronary atherosclerosis Grade 3 or higher, there were five deaths attributed to the arterial disease. In I of these, the mitral valve had been removed for insufficiency resulting from antecedent myocardial infarction. A complication of the prosthesis was the cause of death in 13 of the 36 cases; this was the largest subdivision of causes of death, conforming with observations of others. 1 t Thrombosis in relation to the graft was common but not a cause of death in all. This process, when present in significant degree, was responsible either for malfunction of the prosthesis (5 cases) or systemic embolism (4 cases). .Mural thrombosis of the left atrium was commonly present in the 9 cases in which significant thrombi were present on the
The Journol of
262
Joassin and Edwards
Thorocic ond Cordiovosculor Surgery
prosthesis. The basis for atrial thrombosis may have been compounded of the changes incident to the primary disease and the stasis that resulted from malfunction of the prosthesis." While bacterial endocarditis is a recognized early complication of valve replacement, it is significant that this condition may occur as a late phenomenon. 4, 8, 13-16 Four of the 36 patients in this study exhibited this condition. The basis for bacterial endocarditis may primarily be bland thrombosis which sets the stage for infection in the event of bacteremia. It is of interest that no cases of bacterial endocarditis were observed in our' earlier study dealing with early (less than 1 month) postoperative deaths, while 4 patients (11 per cent) in the current study developed this complication. The postoperative interval varied from 11/2 to 38 months. The concept that antibiotic prophylactic therapy should be given to patients with prosthetic valves who are to have such procedures as dental extraction or prostatectomy is justified by our experience. Summary
A pathologic study was done upon 36 adult patients who had had only the mitral valve replaced by a prosthesis, who had lived longer than 1 month, and from whom, upon death, the specimen of heart became available for study. Eleven of the patients lived for periods between 2 and 6 years. Five of the patients died of noncardiac causes. Of the remaining 31, each died of cardiac disease. Three categories of cardiac causes of death were identified. These and the number of cases per category are as follows: (1) residual effect or complication of the operation, 11 cases; (2) associated cardiac disease, 7 cases; and (3) complications of the prosthesis, 13 cases. Of the latter group, the postoperative interval was between 1 and 7 months in 4 cases, between 8 and 23 months in 3 cases, and more than 2 years in 6 cases. Thrombosis in relation to the prosthesis with resulting malfunction of the prosthesis or systemic
embolism was observed in 9 instances, while bacterial endocarditis in relation to the seat of the prosthesis was seen in 4 instances. Coronary atherosclerosis of significant degree (more than 50 per cent narrowing of the arterial lumen at one or more of the segments) was observed in 9 (22 per cent) of the cases. Among these, death was attributed to a complication of the associated coronary disease in 5. REFERENCES
2 3
4
5
6
7
8
9 10
11
Joassin, A, and Edwards, J. E.: Causes of Death Within 30 Days of Mitral Valvular Replacement: Analysis of 93 Cases, in Brest, A N., editor: Clinical-Pathologic Correlations -Cardiovascular Clinics, Philadelphia, F. A. Davis Company. In press. Hughes, R. K.: Complications of Starr-Edwards Mitral Valve Replacement, J. THORAC. CARDIOVASC. SURG. 49: 731, 1965. Danielson, G. K., Cooper, E., and Tweeddale, D. N.: Circumflex Coronary Artery Injury During Mitral Valve Replacement, Ann. Thorac. Surg. 4: 53, 1967. Roberts, W. C., and Morrow, A G.: Late Postoperative Pathological Findings After Cardiac Valve Replacement, Circulation 35, 36: 48, 1967 (Suppl. I). Morrow, A. G., Oldham, H. N., Elkins, R. c., and Braunwald, E.: Prosthetic Replacement of the Mitral Valve: Preoperative and Postoperative Clinical and Hemodynamic Assessments in 100 Patients, Circulation 35: 962, 1967. Starr, A, Herr, R. H., and Wood, J. A.: Mitral Replacement: Review of Six Years' Experience, J. THORAC. CARDIOVASC. SURG. 54: 333, 1967. Beall, A. C., Jr., Bloodwell, R. D., Bricker, D. L., Okies, J. E., Cooley, D. A., and De Bakey, M. E.: Prosthetic Replacement of Cardiac Valves: Five and One-Half Years' Experience, Am. J. Cardiol. 23: 250, 1969. Spencer, R. C., Reed, G. E., Clauss, R. H., Tice, D. A, and Reppert, E. H.: Cloth-Covered Aortic and Mitral Valve Prostheses: Experiences With 113 Patients, J. THORAC. CAROIOVASCo SURG. 59: 92, 1970. Starr, A: Mitral Valve Replacement With Ball Valve Prostheses, Br. Heart J. 33: 47, 1971. Litwak, R. S., Silvay, J., Gadboys, H. L., Lukban, S. B., Sakurai, H., and Castro-Blanco, J.: Factors Associated With Operative Risk in Mitral Valve Replacement, Am. J. Cardiol. 23: 335, 1969. Niles, N. R., and Sandilands, J. R.: Pathology of Heart Valve Replacement Surgery: Au-
Volume 65 Number 2
Death after mitral valve replacement
263
Februory. 1973
topsies of 62 Patients With Starr-Edwards Prostheses, Chest 56: 373, 1969. 12 Roberts, W. C., and Morrow, A. G.: Mechanisms of Acute Left Atrial Thrombosis After Mitral Valve Replacement: Pathologic Findings Indicating Obstruction to Left Atrial Emptying, Am. J. Cardio!. 18: 497, 1966. 13 Goodman, J. S., Schaffner, W., Collins, H. A., Battersby, E. J., and Koenig, M. G.: Infection After Cardiovascular Surgery: Clinical Study Including Examination of Antimicrobial Prophylaxis, N. Eng!. J. Med. 278: 117, 1968.
14 Killen, D. A., Collins, H. A., Koenig, M. G., and Goodman, J. S.: Prosthetic Cardiac Valves and Bacterial Endocarditis, Ann. Thorac. Surg. 9: 238, 1970. 15 Shafer, R. B., and Hall, W. H.: Bacterial Endocarditis Following Open Heart Surgery, Am. J. Cardio!. 25: 602, 1970. 16 Sande, M. A., Johnson, W. D., Jr., Hook, E. W., and Kaye, D.: Sustained Bacteremia in Patients With Prosthetic Cardiac Valves, N. Eng!. J. Med. 286: 1067, 1972.
Ithen causes an earlier communication, we' described of death among 93 patients who died less than 30 days after replacement of the mitral valve for various types of mitral valve disease. This communication concerns itself with 36 cases of mitral valve replacement in which the patients survived for at least 30 days after the operation. Eleven of the patients survived between 2 and 6 years following the operation. Materials and methods Thirty-six patients, in each of whom the mitral valve alone was replaced by a prosthesis and in whom death occurred 30 days or more from the time of operation, were reviewed. All cases obtained during a period from 1961 through 1972 which met the above-mentioned criteria were included, the principal sources being the University of Minnesota Hospitals and the United Hospitals, Inc.-Miller Division (formerly the From the Departments of Pathology. United Hospitals, Inc. -Miller Division, St. Paul, Minn. 55102, and University of Minnesota, Minneapolis, Minn. 55455. This study was supported by Public Health Service Research Grant 5 ROI HL05694 and Research Training Grant 5 TOI HL05570 from the National Heart and Lung Institute. Received for publication July 17, 1972. ·Supported by a grant from Conseil de la Recherche Medicale du Quebec, Quebec, Canada.
Charles T. Miller Hospital). Fewer cases were obtained from other institutions. All cases from which specimens were received and which fulfilled the criteria mentioned were included. The patients ranged in age from 24 to 72 years and included 21 male and 17 female subjects. The types of mitral valve disease for which the natural valve was replaced by a prosthesis included stenosis of rheumatic nature and mitral insufficiency of various etiologic types; only 1 patient required valve replacement as the result of myocardial infarction. In 7 of the patients with mitral stenosis, a mitral commissurotomy had been done at varying times prior to replacement of the valve. The prostheses varied in design, but in most cases the Starr-Edwards Model 6120, which has a movable ball, was used. In each case, the specimen of heart obtained at autopsy was available and reviewed. In certain cases, more than one pathologic abnormality was observed. These were considered along with the abstract of the clinical features so that one cause of death was named per patient. The causes of death could be grouped into four categories as follows: (1) residual effect or complication of operation, (2) associated disease, ( 3) complication of 255
The Journal of
256
Joassin and Edwards
Thoracic and Cardiovascular Surgery
Table I. Summary of data in 36 cases studied Corollary atherosclerosis Postoperative interval (mo.)
Cause of death
No. of cases
Residual effect or complication of operation
11
11
9 3
9 3 1 5 1
Cardiac Myocardial failure Left ventricular outflow obstruction Dehiscence Cerebral Hepatic Associated disease Cardiomyopathy Coronary atherosclerosis Complication of prosthesis Thrombosis with stenosis Thrombosis with embolism Bacterial endocarditis Noncardiac disease Total
prosthesis, and (4 ) non-cardiac disease. These categories are defined below. The category of residual effect or complication of operation included those conditions, such as persistent myocardial failure following operation, malposition of prosthesis causing left ventricular outflow obstruction, dehiscence of the seat of the prosthesis, and those conditions secondarily related to the operation, such as cerebral anoxia and hepatitis. Associated disease included those conditions present prior to the operation which were of such significance as to be considered the basis for death. Complications of prothesis included (1) thrombosis in relation to the prosthesis, serving either to make the prosthesis stenotic or to be a basis for systemic arterial embolism, and (2) bacterial endocarditis in relation to the prosthesis. Observations
Among the 36 cases studied, the causes of death were distributed as follows: residual effect or complication of operation, 11 cases (30 per cent); associated disease, 7
1-7
I
8-23
o
I
24-72
o
o
o o
1
o o o
o o o
7 2 5
2
2
3
13 5 4
4 1 I 2
5
2
36
19
1
5 1 1
4
o
2
o o
o
o
2
Grade 21 Grade 3 or less or more 10 8 3 1 4 1 1
2 2
I
o
3
6
11
1 1 1
3 2 I
5 3 3
2
4
11
27
2
6
1 1
o o 1
o
o 5
o 5
2
o I I
9
cases (20 per cent); complication of prosthesis, 13 cases (36 per cent); and noncardiac diseases, 5 cases (14 per cent). Table I lists the causes of death, the interval of postoperative survival, and the grade of coronary atherosclerosis. Among the 36 patients, death occurred between the first and seventh postoperative months in 19 cases, between 8 months and 2 years in 6 cases, and between 2 and 6 years in II cases. Among the latter, 4 patients lived into the sixth postoperative year. The causes of death of the 19 patients who died between 1 and 7 months after operation were distributed fairly uniformly among the several categories of causes of death while, among the group with longest survival times, the common cause of death was a complication of the prosthesis. Residual effect or complication of operation. In each of the 11 patients in whom the cause of death was a residual effect or complication of the operation, death occurred less than 7 months after the operation. This group was subdivided according to the site of residual effect or complication of operation as follows: ( I) cardiac, 9
Volume 65 Number 2
Death after mitral valve replacement
257
February , 1973
cases; (2) cerebral, 1 case; and (3) hepatic, I case. In nine of the cases in which death was attributed to a residual effect or complication of the operation, a cardiac condition was present such as myocardial failure (3 cases), left ventricular outflow obstruction (I case), and dehiscence of the seat of the mitral prosthesis in the absence of bacterial endocarditis (5 cases). Each of the 3 patients with myocardial failure had cardiac hypertrophy, the hearts weighing 630, 700, and 700 grams, respectively. One manifested a low cardiac output after operation. He remained in a state of intractable cardiac failure in spite of vigorous medical treatment and died 6 weeks after operation. The second patient exhibited a stormy postoperative course from which he recovered. Sudden death occurred 5 months postoperatively. At autopsy, the heart, except for being greatly hypertrophied, manifested no unusual features. The coronary arteries were devoid of significant degrees of atherosclerosis. The third patient had shown severe pulmonary hypertension preoperatively (120/ 16 mrn, Hg). After experiencing a continuous state of congestive cardiac failure postoperatively, the patient died 4 months after replacement of the mitral valve. Left ventricular outflow obstruction by the mitral prosthesis was considered the cause of death in I patient. This patient, whose primary condition had been mitral stenosis, died 7 weeks postoperatively. In the absence of bacterial endocarditis, dehiscence of the prosthesis at the lateral aspect of the mitral ring was observed in 5 cases (Fig. I). In each of these cases, mitral insufficiency was the basis for the clinical picture of postoperative heart failure and pulmonary edema . Death occurred 2 months postoperatively in 3 cases and at 6 months and 7 months, respectively, in the other 2. Cerebral disease was the cause of death in I patient. This patient had developed cardiac arrest soon after completion of the operation; although cardiac resuscitation
Fig. 1. Mitral valve prosthesis from above. There is a dehiscence (between arrows) of the valvular prosthesis from the mitral valve ring in the lateral aspect of the valve area. Death resulted from mitral insufficiency and congestive heart failure 2 months after insertion of the prosthet ic valve.
had been accomplished, a cerebral deficit resulted and death occurred 17 weeks postoperatively. Hepatitis was considered to be the cause of death in I case. This complication appeared 4 months after the operation and resulted in death of the patient 2 weeks after onset. Associated disease. Of the 7 patients in whom death appeared to have resulted from diseases associated with the mitral valve disease, the associated diseases were subdivided into two groups: ( 1) cardiomyopathy and (2) coronary atherosclerosis. Cardiomyopathy had been the basis for mitral insufficiency in 2 patients who had undergone mitral valve replacement. The first of these patients died suddenly 3 years postoperatively, while the second developed congestive heart failure I year after operation. He was supported by medical treatment but died 3 years and 8 months postoperatively . In both patients, the myocardium had numerous scars attributed to antecedent myocarditis (Fig. 2). In each of the 36 cases of this study, coronary atherosclerosis as seen in the
The Journal of
25 8
Ioassin and Edwards
Thoracic and Cardiovascular Surgery
PII. 1. Myocarditis. Interior of left ventricle 3 years and 8 months after replacement of the mitral valve for mitral insufficiency associated with chronic myocarditis. Endocardial fibroelastosis is a prominent feature. Death was attributed to the associated changes of antecedent myocarditis.
pathologic specimen was graded as 2 or less or else 3 or more. Grade 2 represented . up to 50 per cent narrowing of the lumen, while Grade 3 signified more than 50 per cent narrowing of the lumen. It is apparent from Table I that, of the 36 patients in this study, 27 had Grade 2 or less coronary atherosclerosis while 9 patients (22 per cent) had coronary atherosclerosis Grade 3 or more. In 4 of the 9 with Grade 3 coronary atherosclerosis, this condition did not appear to contribute to death, while in the remaining 5 patients it was considered to have caused death . Common phenomenon among 5 patients in whom death was attributed to coronary disease was sudden unexpected death . Pathologically, myocardial scarring from earlier myocardial infarction but without evidence of acute ischemic necrosis of myocardial tissue was a characteristic. In 1 of the 5 patients dying of coronary disease, mitral insufficiency resulting from myocardial infarction had been the indication for mitral valve replacement. In another case, in addition to mitral valve replacement for mitral stenosis, a saphenous vein graft was inserted in the coronary arterial system 42
months prior to death . The survival time after operation in the 5 patients whose deaths were attributed to coronary disease was 7 months in 2 patients, between 17 and 20 months in 2, and 42 months in the fifth. Complication of prosthesis. In 13 patients, death was attributed to a complication of the prosthesis. In 9 this took the form of thrombosis, and in 4 death was caused by bacterial endocarditis. Thrombosis. Although superficial thrombosis on or in relation to the seat of the prosthetic valve was commonly found among the entire series of patients, there were 9 cases in which thrombosis represented a major complication and cause of death. In 5 of these, thrombosis was extensive and accounted for obstruction to the inlet of the prosthesis and/or restriction in motion of the ball (Fig. 3) . Congestive heart failure was present in each. Among patients in this group, death occurred Ph, 17, 36, 48, and 60 months after operation. In 4 other cases, thrombosis was the source of major systemic arterial embolism 18, 29, (Fig. 4) , and death occurred 1~, and 60 months after operation. In each case, autopsy revealed thrombi deposited along the atrial and ventricular aspects of the prosthesis. In 3 cases, extensive left atrial mural thrombosis was present as wen. In I of the patients with systemic arterial embolism in additionto thrombi in relation to the prosthesis, a false aneurysm was present in the base of the left ventricle (Fig. 5). This lesion may have been a source of cerebral embolism. Its mouth lay just inferior to the seat of the prosthesis. It is assumed that the basis for the aneurysm was laceration of the left ventricular wall at the time of operation 5 years previously. Bacterial endocarditis. Bacterial endocarditis (Figs. 6 and 7) in relation to the mitral prosthesis was observed in 4 cases, in each of which death was caused by systemic embolism. In 2 of the 4 patients with bacterial endocarditis, an infectious complication or a procedure could be identified as a probable cause of infection. One patient had developed empyema in
Volume 65 Number 2 Februory, 1973
Death after mitral valve replacement
259
FfI. 3. Thrombosis of mitral valve prosthesis 3 years postoperatively. a, Mitral valve prosthesis
viewed from above. The seat of the valve is obscured by thrombotic material which partially encroaches upon the inlet to the valve. b, View from left ventricular aspect shows thrombotic material along the struts and within the cage, thereby restricting motion of the ball.
.!lo.-.
Fig. 4. Photomicrograph of anterior descending coronary artery. Occlusion of lumen by embolus of thrombus upon mitral valve prosthesis . (Hematoxylin and eosin; original magnification x23.)
the early postoperative period and died IIh months after operation, Autopsy revealed gram-positive cocci in the empyema exudate as well as in vegetations near the mitral prosthesis. Multiple emboli to the myocardium were associated with foci of acute myocardial infarction. In another case of bacterial endocarditis,
FIg. 5. Lateral view of left atrium (L.A.) and left ventricle (L.V.) in a patient with mitral valve re-
placement 5 years previously. Thrombotic material is present on the atrial surface of the seat of the valve and along the inlet to the valve. (The ball has been removed from the prosthesis.) At the base of the left ventricle is a false aneurysm (F.A.) which appears to have resulted from laceration of the left ventricle at the time of operation. Thrombotic material in the aneurysm and at the seat of the valve was a potential source for systemic embolism, which was the cause of death.
The Journol of
260
Joassin and Edwards
Thoracic and Cardiovascular Surgery
Fig. 6. Bacterial endocarditis complicating mitral valve replacement. Operation 3 months previously. a, The mitral prosthesis viewed from above. Thrombotic material is present along the atrial aspect of the seat. Probe shows the site of dehiscence of the prosthesis from the mitral ring. b, The mitral valve prosthesis viewed from the left ventricular aspect. Medial to the seat of the valve is a vegetation (between arrows) extending into the ventricular septum and representing a site of invasive bacterial endocarditis. There is a secondary site of infection in the subaortic area (single arrow).
a urethral stricture was noted to be present after the mitral valve replacement. Penicillin was administered prophylactically with each of several therapeutic urethral dilatations. Clinical signs of bacterial endocarditis became apparent several days before death, 38 months after replacement of the mitral valve. At autopsy, both the atrial and ventricular aspects of a disctype prosthesis were found to be covered by thrombi, and adjacent tissue showed signs of bacterial infection (Fig. 7). An additional finding in this case was external compression of the left circumflex artery by suture material used to secure the mitral prosthesis, as described by others.v 3 The related, healed posterobasal infarct of the left ventricle which we found did not appear to have contributed to the death of the patient. Of the 2 remaining patients with bacterial endocarditis, 1 died of embolism to the right coronary artery 11 months after operation. The last patient died 3 months postoperatively of cerebral embolism. Partial dehiscence of the base of the prosthesis was present in this case (Fig. 6). Noncardiac diseases. Five patients were
considered to have died of noncardiac causes. The relationship is questionable in 1, as the patient died of pulmonary embolism 5 years after the operation. Among the remaining 4 patients, 1 died from rupture of a congenital arteriovenous fistula of the brain 2 months postoperatively. One subject committed suicide 6 months after the operation. The third patient died 15 months postoperatively from undifferentiated pulmonary carcinoma, and the last died of Hodgkin's disease 72 months postoperatively. Comment In this study on deaths occurring between 1 month and 6 years after replacement of the mitral valve, the causes of death related to the cardiac disease could be placed into three categories as follows: ( 1) residual effect or complication of the operation, (2) associated disease, and (3) complication of the prosthesis. In general, our observations conform with those of other studies':" on late effects of valve replacement. Death occurring 7 months or more after operation resulted from the various types of death, while all of the deaths
Volume 65 Number 2
Death after mitral valve replacement
261
February. 1973
Fig. 7. Bacterial endocarditis in a case in which a urethral stricture was dilated following mitral valve replacement. Death resulted 38 months after replacement of mitral valve by disctype prosthesis. a. Mitral valve prosthesis viewed from above. The latter is obscured by thrombotic material present over its inlet. Discoloration of the adjacent left atrial wall is a feature of extension of bacterial infection. b, Left ventricle and the mitral valve prosthesis viewed from below. Vegetative material of bacterial endocarditis is deposited along the ventricular aspect of the base of the prosthesis, and similar material extends along the struts of the prosthesis.
resulting from a residual effect or complication of the operation occurred from 1 to 7 months after operation. Among the 11 patients dying of a residual effect or complication of the operation, 3 had marked cardiomegaly, a condition in itself which may have disturbing prognostic significance.w
The incidence of significant coronary atherosclerosis (Grade 3) was 22 per cent in this series of patients who survived at least 1 month following operation. The incidence of coronary deaths in our series was about the same as in the study of Starr." A higher figure of 33 per cent incidence of coronary atherosclerosis Grade 3 or more was observed in our- earlier study involving patients who failed to live longer than 1 month after mitral valve replacement. The difference may be an indication of the greater hazard of the procedure to the sub-
ject with significant atherosclerosis than to the patient with lesser degrees of this condition. Among the 9 patients with coronary atherosclerosis Grade 3 or higher, there were five deaths attributed to the arterial disease. In I of these, the mitral valve had been removed for insufficiency resulting from antecedent myocardial infarction. A complication of the prosthesis was the cause of death in 13 of the 36 cases; this was the largest subdivision of causes of death, conforming with observations of others. 1 t Thrombosis in relation to the graft was common but not a cause of death in all. This process, when present in significant degree, was responsible either for malfunction of the prosthesis (5 cases) or systemic embolism (4 cases). .Mural thrombosis of the left atrium was commonly present in the 9 cases in which significant thrombi were present on the
The Journol of
262
Joassin and Edwards
Thorocic ond Cordiovosculor Surgery
prosthesis. The basis for atrial thrombosis may have been compounded of the changes incident to the primary disease and the stasis that resulted from malfunction of the prosthesis." While bacterial endocarditis is a recognized early complication of valve replacement, it is significant that this condition may occur as a late phenomenon. 4, 8, 13-16 Four of the 36 patients in this study exhibited this condition. The basis for bacterial endocarditis may primarily be bland thrombosis which sets the stage for infection in the event of bacteremia. It is of interest that no cases of bacterial endocarditis were observed in our' earlier study dealing with early (less than 1 month) postoperative deaths, while 4 patients (11 per cent) in the current study developed this complication. The postoperative interval varied from 11/2 to 38 months. The concept that antibiotic prophylactic therapy should be given to patients with prosthetic valves who are to have such procedures as dental extraction or prostatectomy is justified by our experience. Summary
A pathologic study was done upon 36 adult patients who had had only the mitral valve replaced by a prosthesis, who had lived longer than 1 month, and from whom, upon death, the specimen of heart became available for study. Eleven of the patients lived for periods between 2 and 6 years. Five of the patients died of noncardiac causes. Of the remaining 31, each died of cardiac disease. Three categories of cardiac causes of death were identified. These and the number of cases per category are as follows: (1) residual effect or complication of the operation, 11 cases; (2) associated cardiac disease, 7 cases; and (3) complications of the prosthesis, 13 cases. Of the latter group, the postoperative interval was between 1 and 7 months in 4 cases, between 8 and 23 months in 3 cases, and more than 2 years in 6 cases. Thrombosis in relation to the prosthesis with resulting malfunction of the prosthesis or systemic
embolism was observed in 9 instances, while bacterial endocarditis in relation to the seat of the prosthesis was seen in 4 instances. Coronary atherosclerosis of significant degree (more than 50 per cent narrowing of the arterial lumen at one or more of the segments) was observed in 9 (22 per cent) of the cases. Among these, death was attributed to a complication of the associated coronary disease in 5. REFERENCES
2 3
4
5
6
7
8
9 10
11
Joassin, A, and Edwards, J. E.: Causes of Death Within 30 Days of Mitral Valvular Replacement: Analysis of 93 Cases, in Brest, A N., editor: Clinical-Pathologic Correlations -Cardiovascular Clinics, Philadelphia, F. A. Davis Company. In press. Hughes, R. K.: Complications of Starr-Edwards Mitral Valve Replacement, J. THORAC. CARDIOVASC. SURG. 49: 731, 1965. Danielson, G. K., Cooper, E., and Tweeddale, D. N.: Circumflex Coronary Artery Injury During Mitral Valve Replacement, Ann. Thorac. Surg. 4: 53, 1967. Roberts, W. C., and Morrow, A G.: Late Postoperative Pathological Findings After Cardiac Valve Replacement, Circulation 35, 36: 48, 1967 (Suppl. I). Morrow, A. G., Oldham, H. N., Elkins, R. c., and Braunwald, E.: Prosthetic Replacement of the Mitral Valve: Preoperative and Postoperative Clinical and Hemodynamic Assessments in 100 Patients, Circulation 35: 962, 1967. Starr, A, Herr, R. H., and Wood, J. A.: Mitral Replacement: Review of Six Years' Experience, J. THORAC. CARDIOVASC. SURG. 54: 333, 1967. Beall, A. C., Jr., Bloodwell, R. D., Bricker, D. L., Okies, J. E., Cooley, D. A., and De Bakey, M. E.: Prosthetic Replacement of Cardiac Valves: Five and One-Half Years' Experience, Am. J. Cardiol. 23: 250, 1969. Spencer, R. C., Reed, G. E., Clauss, R. H., Tice, D. A, and Reppert, E. H.: Cloth-Covered Aortic and Mitral Valve Prostheses: Experiences With 113 Patients, J. THORAC. CAROIOVASCo SURG. 59: 92, 1970. Starr, A: Mitral Valve Replacement With Ball Valve Prostheses, Br. Heart J. 33: 47, 1971. Litwak, R. S., Silvay, J., Gadboys, H. L., Lukban, S. B., Sakurai, H., and Castro-Blanco, J.: Factors Associated With Operative Risk in Mitral Valve Replacement, Am. J. Cardiol. 23: 335, 1969. Niles, N. R., and Sandilands, J. R.: Pathology of Heart Valve Replacement Surgery: Au-
Volume 65 Number 2
Death after mitral valve replacement
263
Februory. 1973
topsies of 62 Patients With Starr-Edwards Prostheses, Chest 56: 373, 1969. 12 Roberts, W. C., and Morrow, A. G.: Mechanisms of Acute Left Atrial Thrombosis After Mitral Valve Replacement: Pathologic Findings Indicating Obstruction to Left Atrial Emptying, Am. J. Cardio!. 18: 497, 1966. 13 Goodman, J. S., Schaffner, W., Collins, H. A., Battersby, E. J., and Koenig, M. G.: Infection After Cardiovascular Surgery: Clinical Study Including Examination of Antimicrobial Prophylaxis, N. Eng!. J. Med. 278: 117, 1968.
14 Killen, D. A., Collins, H. A., Koenig, M. G., and Goodman, J. S.: Prosthetic Cardiac Valves and Bacterial Endocarditis, Ann. Thorac. Surg. 9: 238, 1970. 15 Shafer, R. B., and Hall, W. H.: Bacterial Endocarditis Following Open Heart Surgery, Am. J. Cardio!. 25: 602, 1970. 16 Sande, M. A., Johnson, W. D., Jr., Hook, E. W., and Kaye, D.: Sustained Bacteremia in Patients With Prosthetic Cardiac Valves, N. Eng!. J. Med. 286: 1067, 1972.