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Prosthetic heart valve replacement in children
J
THORAC CARDIOVASC SURG
1987;93:80-5
Prosthetic heart valve replacement in children Results and follow-up of 273 patients We report the results and long-term follow up in 273 children (aged 2 to 16 years) who underwent prosthetic valve replacement. Mechanical valves(mostly Starr-Edwards) were used in almost all, and in 62 children more than one valve was replaced. Operative mortality was 4.7%. Actuarial survival curves (including hospital mortality) indicate a 86% survival rate at 5 years and 75% at 10 years. For isolated mitral valve prostheses (the largest subgroup~ the figures are 87% at 5 years and 82% at 10 and 15 years. The main complication was thromboembolism, which occurred at a linearized rate of 2.7 per 100 patient-years. Actuarial curves indicate that 88% of patients are embolus free at 5 years, and 77% at 10 years. No patient with aortic valve replacement only had an embolism. Five of eight tricuspid prostheses thrombosed. Patients given aspirin and dipyridamole only did not have a higher rate of thromboembolic events than those given warfarin. There were five cases of endocarditis (two fatal) and four of dehiscence. No patient so far has needed replacement of a prosthesis because of somatic growth. Thus valve replacement can be performed with low mortality in children, and with satisfactory long-term survival. Thromboembolism remains a significant problem, although it appears to be less common than in adults. In this study, treatment with antiplatelet drugs only did not carry a higher rate of thromboembolic events than did treatment with warfarin.
A. El Makhlouf, M.D., B. Friedli, M.D., I. Oberhansli, M.D., J.-C. Rouge, M.D., and B. Faidutti, M.D., Geneva, Switzerland
Although conservative surgery is the preferred treatment for valvular lesions in children, prosthetic replacement is sometimes unavoidable. This is particularly true in rheumatic heart disease, because scarring and calcification often make reconstruction of a valve impossible. Rheumatic fever is uncommon in Western countries, but remains a major problem in developing countries, where children may have severe rheumatic valvular disease at a young age. Many of the children operated on in our hospital were from North Africa or the Middle East. We report the surgical results and long-term follow-up in a large group of children with valve prostheses, the majority from developing countries.
From the Pediatric Cardiac Unit and Division of Cardiovascular Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Received for publication Dec. 16, 1985. Accepted for publication Feb. 24, 1986. Address for reprints: Beat Friedli, M.D., Unite de Cardiologie Pediatrique, Clinique Universitaire de Pediatrie, Hopital Cantonal Universitaire, CH-1211 Geneve, 4 Switzerland.
80
Patients and methods From 1969 to 1984,273 children underwent prosthetic valve replacement at our institution. Their ages ranged from 2 to 15 years (mean 12 years). One hundred twenty-six (46%) were boys, and 147 (54%) girls. Two hundred fifty-three patients had rheumatic valvular disease (all but one of these were from Africa or the Middle East), 19 had congenital valve anomalies, and one had endomyocardial fibrosis. Preoperatively, 76% had New York Heart Association (NYHA) Class III or IV disease, and the remaining patients Class II with either severe pulmonary hypertension or severe cardiomegaly. In 211 children a single valve was replaced (176 mitral, 34 aortic, one tricuspid); two valves were replaced in 60 (55 mitral and aortic, five mitral and tricuspid); and in two, three valves were replaced (mitral, tricuspid, and aortic). Table I lists the prostheses used. These were almost exclusively mechanical valves, the Starr-Edwards prosthesis being most often implanted (226). Bjork-Shiley prostheses (58) were used in the aortic position essentially; only six biologic valves (Hancock) were used. The majority of prostheses were adult size, but some small
Volume 93 Number 1
Prosthetic heart valve replacement in children
January 1987
81
.-.-,-.-.
Percent
100
. . . . . . i ............
80
-.-.
I
0
-.-1- \ 60
'0__ +_-----
40
20
1
rno
3
5
7
Years
9
11
15
13
Fig. 1. Actuarial survival curve for all recipients of heart valve prostheses. Curve includes operative mortality. Five-year survival rate is 86% and 10 year survival rate 75%. Total number followed up at 5 years is 120, at 10 years 22; only seven have been followed up longer than II years, and the drop at 12 years is therefore of questionable significance (large standard error).
prostheses were implanted (Starr size 0 or 1 in 15 patients, and Bjork 17 or 19 mm in 20 children). From the third postoperatiave day, the children received treatment aimed at decreasing the risk of emboli: Those in whom prothrombin time could be regularly checked received warfarin sodium (Coumadin); those living far from major hospitals received aspirin (20 rug/kg/day) and dipyridamole (5 tug] kg/day). Follow-up was done by local hospitals and physicians, whoreturned questionnaires, and by social workers from the Third World organization Terre des Hommes, located in the respective countries, who maintained contact with the patients and reported back at regular intervals. Actuarial survival curves (and event-free percentages) were calculated according to the method of Anderson and associates.I
Results Operative mortality. Four patients died during the operation, and nine within 1 month after the operation, for an early mortality of 4.7%. Most of these patients had end-stage heart failure from rheumatic heart disease.
In survivors, improvement after operation was fast and often spectacular, the children returning to normal activities within 1 or 2 months. Long-term follow-up. Of the 260 survivors,48 (18%)
Table I. Prostheses implanted in 273 children Starr-Edwards Bjork-Shiley S1. Jude Medical Hancock
Mitral
Aortic
Tricuspid
Total
231 1
32 52 7
3 5
266 58 7 ......Q 337
6
patients were lost to follow-up; the remaining patients were observed for a total of 887 patient-years (mean 4.2 years, maximum 15 years). There were 23 late postoperative deaths, 2 months to 12 years after operation. Fig. 1 shows actuarial survival curves for the whole group, and Fig. 2 for mitral, aortic, and mitral plus aortic replacement. Cumulative survival rate is 86% ± 3% at 5 years, and 75% ± 5% at 10 years for the total group (operative mortality included). For isolated mitral prostheses, the figures are 87% ± 3% at 5 years and 82% ± 4% at 10 years, but with no further death to 15 years. For patients with Starr-Edwards mitral prostheses (excluding the seven Hancock and Bjork-Shiley prostheses), survival is slightly better: 89% ± 3% at 5 years, and 83% ± 4% at 10 years. For isolated aortic valve replacement, there was 94% ± 4% survival at 5 years. The sharp drop at 7 years is related to one death in a very small cohort followed, and cannot be considered significant (very large standard error of 26%). In patients with mitral plus aortic valve replacement, the
82
The Journal of Thoracic and Cardiovascular Surgery
EI Makhlouf et al.
Percent 100
e_ ' !"---'
·:::::.... -·c:::::::::: . _·-I-· <, .---- - .
80
-
1"
"'"_:~~\
,, , ,,
60
:=!-J_:=:=:=:= I
-.- - - ...
40 e Mitral
• Aortic
20
" Mitral + Aortic
1
mo
3
5
7
Years
9
11
13
15
Fig. 2. Actuarial survival curves (including operative mortality) given separately for mitral, aortic, and mitral plus aortic valve replacement. Probability of survival for patients with mitral prostheses is 82% at 10 and 15 years, for patients with mitral plus aortic prostheses 77%. For isolated aortic prostheses, the sharp drop occurring between 7 and 8 years is the result of one death in a very small cohort followed, and is therefore of questionable significance (very large standard error).
Table Il, Causes of late deaths Thrombosis, embolism Heart failure Bacterial endocarditis Prosthetic valve detachment Noncardiac Unknown
8 5 2 1 2
..2 23
survival rate at 10 years is 77%. The causes of late death are listed in Table II. Thromboembolic events were the most common cause of late deaths, followed by heart failure.
Complications. Thromboembolic events. There were 24 thromboem-
bolic events (linearized rate 2.7 per 100 patient-years). Clinically significant embolic episodes occurred 18 times; eight accidents were fatal. Thrombotic obliteration of a valve occurred six times, four times in tricuspid prostheses; thus four of seven survivors of tricuspid valve replacement had thrombosis and died. Emboli occurred in the central nervous system in 16 patients, coronary artery in one (with myocardial infarction), and retinal artery in one. Four of the patients with embolic accidents to the central nervous system had significant neurologic sequelae; three had minimal residua. Two patients had more than one embolic episode.
Figs. 3 and 4 show actuarial curves indicating percentage of patients free from thromboembolic events. At 5 years, 88% ± 3% are free of thromboemboli, and at 10 and 15 years 77% ± 6%. None of the patients with an isolated aortic prosthesis had a thromboembolic accident. Of patients with isolated mitral prosthesis, 81% ± 6% are free of thromboemboli at 10 years (80% if Starr-Edwards prostheses are considered exclusively); of patients with mitral plus aortic prostheses, 78% ± 8% are event free. These subgroups show higher event-free percentages than the total group because they do not include patients with tricuspid prosthesis, in whom thrombosis was extremely frequent. Anticoagulants and thromboemboli. Eighty-three children received warfarin anticoagulants on a regular basis. There were seven (8.4%) thromboembolic events in this group; the linearized rate is 2.3 per 100 patientyears. One hundred fifty children received treatment to reduce platelet adhesiveness (aspirin and dipyridamole). Thirteen (8.7%) patients had thromboemboli; the linearized rate is 2.3 per 100 patient-years. Twenty-one patients have stopped taking medication for various reasons, and four (19%) had emboli. The differences between these groups are statistically not significant (by the chi square test), for the latter group (no treatment) because of the small sample size. Two patients had severe hemorrhage: One had multiple hematomas and nose bleeds while taking warfarin,
Volume 93 Number 1 January 1987
Prosthetic heart valve replacement in children
Percent 100 _ . _
·_1I-·___
80
·-t-·-.
83
1-·-·-·-·-1
- - ·<,
60
40
20
3
5
7
Years
9
11
13
15
Fig. 3. Actuarial curves indicating percentage of patients free from thromboembolism (total group). At 5 years, 88% are embolus free, and at 10 years 77%.
. "--._1 . y--.
Percent 100,/"'ll;:::-------- - - - - - - - ~.
80
--.
-·-·-r-·-·"" f 1-·-·-·-·-·-f-·_·-·-·-f I
~.
e-
""
T
-e-e-.
60
• Mitral
40
• Aortic • Mitral + Aortic
20
3
5
7
Years
9
11
13
15
Fig. 4. Actuarial curves indicating percentage of patients free from thromboembolism, given separately for recipients of mitral prostheses, aortic prostheses, and mitral plus aortic valve replacement. None of the patients with aortic valve replacement only had a thromboembolic accident. At 10 years, 81% of patients with mitral prostheses are embolus free, versus 78% of patients with mitral plus aortic prostheses.
and the other had massive gastric hemorrhage while taking aspirin. Both recovered. Endocarditis. There were five cases of bacterial endocarditis, which proved fatal in two patients. One patient died despite two reoperations; the three others received medical treatment only, and recovered. The microorganism is known in three patients: Streptococ-
cus epidermidis, Haemophilus parainfluenzae, and a-hemolytic Streptococcus, respectively. In one patient endocarditis occurred shortly after, and was probably related to, the operation; in another, a dental abscess was found containing the same germ; and in the remaining patients the site of entry was unknown. Valve detachment and degeneration. Four prosthetic
The Journal of'
84
El Makhlouf et aJ.
valves became partially detached. One patient died, having refused reoperation; the other three underwent successful reoperation. Two Hancock prostheses degenerated, calcified, and thrombosed. One patient died, and the other underwent successful reoperation. Discussion Valve replacement in children can be performed with low mortality." However, implanting artificial valves in a young population poses a number of problems: (1) Because of the long life expectancy, durability of the valve is of major concern. (2) Anticoagulant treatment, recommended for all bearers of mechanical valves, may be hazardous in children who are physically very active, and requires regular controls not always easy to obtain in developing countries. (3) "Outgrowing" of a valve is a concern when small-diameter prostheses must be implanted. There is no doubt that bioprostheses should no longer be used in children, because degeneration and calcification occur rapidly in these valve substitutes"; valve survival at 7 years is onlyI8%.7 Mechanical prostheses, on the other hand, especially Starr-Edwards prostheses, have an excellent record of durability9-11 and are virtually indestructible. This is the main reason why we continue to use Starr-Edwards valves in our institution. However, there are valve-related complications, the most important being valve thrombosis and embolism, Fortunately, it appears that thromboembolism is less common in children than in adults with valve prostheses. In adults, about four to six thromboembolic episodes per 100 patient-years are reported for mitral prostheses, the figures being lower for aortic prostheses.10-13 In children, some groups report a very low incidence of thromboemboli: 0.8 to 1.7 per 100 patient-years.s-" In our series, the linearized rate of 2.7 per 100 patient-years is somewhat higher; still, with mitral valve replacement 81% of patients are embolus free at 10 years, a percentage that has not been described in adult patients. No child with aortic valve replacement only had an embolus; this is in striking contrast to the data reported by the Mayo Clinic, where the risk of thromboemboli was higher in children with aortic than with mitral prostheses." Patients with multiple valve replacement have a somewhat higher incidence of thromboemboli; but by far the highest risk of thrombosis is encountered in tricuspid valve replacement (four of seven in our series). Tricuspid valve replacement is therefore avoided in our institution. Anticoagulant therapy is a major problem in children,
Thoracic and Cardiovascular Surgery
especially from Third World countries. Whenever it is evident that regular prothrombin time tests cannot be performed, we prescribe dipyridamole and aspirin as the only treatment. In our large series, we found that these children do not have more thromboemboli than patients given warfarin. However, we do not know how many children receiving warfarin have consistantly optimal levels of prothrombin time. It has been shown that only patients with optimal control are effectively protected from emboli by warfarin"; thus the incidence of emboli may be further reduced in children if constantly efficient anticoagulation is achieved. The fact that only one of our patients had anticoagulant-related hemorrhage may be an indication that many children received suboptimal doses of warfarin. Other complications have been comparatively rare. There were five cases of endocarditis, of which three responded to medical therapy. Valve dehiscence has also been uncommon, and can be treated effectively by reoperation. The problem of "outgrowing" the prosthesis deserves some comment. When very small valve prostheses must be implanted, replacement with a larger one becomes mandatory as the child grows.16,17 Thus far none of our children has required another operation for this reason. Indeed, the left side of the heart was markedly dilated in most patients, and a Starr-Edwards No.2 (or larger) mitral prosthesis could be implanted in the vast majority aged 4 years or older. Of the few children who received No. 1 prostheses, some may require reoperation. One of. these children, operated on at age 2 years, underwent recatheterization 6 years and again 9 years after implantation of a Starr-Edwards No.1 mitral prosthesis;onlya minimal gradient was found. The problem of outgrowing the prosthesis may be more important in our patients with small aortic prostheses, because Bjork 17 and 19 mm valves will become "stenotic" when the children reach adulthood. Replacement of aortic prostheses can be done without major problems." We conclude from this study that valve replacement in children can be done with a low operative mortality and satisfactory late survival; indeed, 10 years after operation, 80% of those who left the hospital are expected to be alive. Thromboembolism is a problem in patients with mitral or multiple valve replacement; however, the complication is less frequent than in adults, even in children receiving no warfarin anticoagulation but only antiplatelet drugs. Tricuspid prostheses havea very high rate of thrombosis and should be avoided whenever possible. Although children with advanced rheumatic heart
Volume 93 Number 1 January 1987
disease benefit enormously from valve replacement, the ultimate solution to this serious problem in Third World countries is eradication of rheumatic fever. REFERENCES
2
3 4
5
6
7
8
9
Anderson RP, Bonchek LI, Grunkemeier GL, Lambert LE, Starr A: The analysis and presentation of surgical results by actuarial methods. J Surg Res 16:224-230, 1974 John S, Bashi VV, Jairaj PS, Muralidharan S, Ravikumar E, Sathyamoorthy I, Babuthaman C, Krishnaswamy S, Cherian G, Sukumar IP: Mitral valve replacement in the young patient with rheumatic heart disease. J THORAC CARDIOVASC SURG 86:209-216, 1983 Berg T, Keck EW: Mitral- und Aortenklappenersatz im KindesaIter. Z Kardiol 73: 173-180, 1984 Friedli B, Friedli GM, Ben Ismail M, Rouge JC, Hahn Ch, Faidutti B: Remplacement valvulaire chez I'enfant. Resultats et suites eloigneeschez 171 operes, Schweiz Med Wochenschr 111: I044-1048, 1981 Thandroyen FT, Witthon IN, Pirie D, Rogers MA, Mitha AS: Severe calcification of glutaraldehyde preserved porcine xenografts in children. Am J Cardiol 45:690-696 1980 ' Silver MM, Pollock J, Silver MD, Williams WG, Trusler GA: Calcification in porcine xenograft valves in children. Am J Cardiol 45:685-689, 1980 Antunes MJ: Bioprosthetic valve replacement in children. Long term follow-up of 135 isolated mitral valve implantations. Eur Heart J 5:913-918, 1984 Attie F, Kuri J, Zanoniani C, Renteria V, Buendia A, Obseyevitz J, Lopez-Soriano F, Garcia-Cornejo M, Martinez-Rios MA: Mitral valve replacement in children with rheumatic heart disease. Circulation 64:812-817,1981 McGoon M, Fuster V, McGoon DC, Pumphrey CW, Pluth JR, Elveback LR: Aortic and mitral valve incompe-
Prosthetic heart valve replacement in children
85
tence. Long-term follow-up of patients treated with the Starr-Edwards prostheses. J Am Coli Cardiol 3:930-938, 1984 10 Miller DC, Oyer PE, Mitchell RS, Stinson EB, Jamieson SW, Baldwin JC, Shumway NE: Performance characteristics of the Starr-Edwards Model 1260 aortic valve prosthesis beyond ten years. J THORAC CARDIOVASC SURG 88:193-207,1984 11 Miller DC, Oyer PE, Stinson EB, Reitz BA, Jamieson SW, Baumgartner WA, Mitchell RS, Shumway NE: Ten to fifteen year reassessment of the performance characteristics of the Starr-Edwards Model 6120 mitral valve prosthesis. J THoRAc CARDIOVASC SURG 85: 1-20, 1983 12 Edmunds LH: Thromboembolic complications of current cardiac valvular prostheses. Ann Thorac Surg 34:96-106, 1982 13 Fuster V, Pumphrey CW, McGoon MD, Chesebro JH, Pluth JR, McGoon DC: Systemic thromboembolism in mitral and aortic Starr-Edwards prostheses. Circulation 66:Suppl 1:157-161, 1982 14 Schaff HV, Danielson GK, Di Donato RM, Puga FJ, Mair DD, McGoon DC: Late results after Starr-Edwards valve replacement in children. J THoRAc CARDIOVASC SURG 88:583-589, 1984 15 Friedli B, Aerichide N, Grondin P, Campeau L: Thromboembolic complications of heart valve prostheses. Am -. Heart J 81:701-708,1971 16 Williams WG, Pollock JC, Geiss DM, Trusler GA, Fowler RS: Experience with aortic and mitral valve replacement in children. J THoRAc CARDIOVASC SURG 81:326-333, 1981 17 Friedman S, Edmunds LH Jr, Cuaso CC: Long term mitral valve replacement in young children. Influence of somatic growth on prosthetic valve adequacy. Circulation 57:981-986, 1978
THORAC CARDIOVASC SURG
1987;93:80-5
Prosthetic heart valve replacement in children Results and follow-up of 273 patients We report the results and long-term follow up in 273 children (aged 2 to 16 years) who underwent prosthetic valve replacement. Mechanical valves(mostly Starr-Edwards) were used in almost all, and in 62 children more than one valve was replaced. Operative mortality was 4.7%. Actuarial survival curves (including hospital mortality) indicate a 86% survival rate at 5 years and 75% at 10 years. For isolated mitral valve prostheses (the largest subgroup~ the figures are 87% at 5 years and 82% at 10 and 15 years. The main complication was thromboembolism, which occurred at a linearized rate of 2.7 per 100 patient-years. Actuarial curves indicate that 88% of patients are embolus free at 5 years, and 77% at 10 years. No patient with aortic valve replacement only had an embolism. Five of eight tricuspid prostheses thrombosed. Patients given aspirin and dipyridamole only did not have a higher rate of thromboembolic events than those given warfarin. There were five cases of endocarditis (two fatal) and four of dehiscence. No patient so far has needed replacement of a prosthesis because of somatic growth. Thus valve replacement can be performed with low mortality in children, and with satisfactory long-term survival. Thromboembolism remains a significant problem, although it appears to be less common than in adults. In this study, treatment with antiplatelet drugs only did not carry a higher rate of thromboembolic events than did treatment with warfarin.
A. El Makhlouf, M.D., B. Friedli, M.D., I. Oberhansli, M.D., J.-C. Rouge, M.D., and B. Faidutti, M.D., Geneva, Switzerland
Although conservative surgery is the preferred treatment for valvular lesions in children, prosthetic replacement is sometimes unavoidable. This is particularly true in rheumatic heart disease, because scarring and calcification often make reconstruction of a valve impossible. Rheumatic fever is uncommon in Western countries, but remains a major problem in developing countries, where children may have severe rheumatic valvular disease at a young age. Many of the children operated on in our hospital were from North Africa or the Middle East. We report the surgical results and long-term follow-up in a large group of children with valve prostheses, the majority from developing countries.
From the Pediatric Cardiac Unit and Division of Cardiovascular Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Received for publication Dec. 16, 1985. Accepted for publication Feb. 24, 1986. Address for reprints: Beat Friedli, M.D., Unite de Cardiologie Pediatrique, Clinique Universitaire de Pediatrie, Hopital Cantonal Universitaire, CH-1211 Geneve, 4 Switzerland.
80
Patients and methods From 1969 to 1984,273 children underwent prosthetic valve replacement at our institution. Their ages ranged from 2 to 15 years (mean 12 years). One hundred twenty-six (46%) were boys, and 147 (54%) girls. Two hundred fifty-three patients had rheumatic valvular disease (all but one of these were from Africa or the Middle East), 19 had congenital valve anomalies, and one had endomyocardial fibrosis. Preoperatively, 76% had New York Heart Association (NYHA) Class III or IV disease, and the remaining patients Class II with either severe pulmonary hypertension or severe cardiomegaly. In 211 children a single valve was replaced (176 mitral, 34 aortic, one tricuspid); two valves were replaced in 60 (55 mitral and aortic, five mitral and tricuspid); and in two, three valves were replaced (mitral, tricuspid, and aortic). Table I lists the prostheses used. These were almost exclusively mechanical valves, the Starr-Edwards prosthesis being most often implanted (226). Bjork-Shiley prostheses (58) were used in the aortic position essentially; only six biologic valves (Hancock) were used. The majority of prostheses were adult size, but some small
Volume 93 Number 1
Prosthetic heart valve replacement in children
January 1987
81
.-.-,-.-.
Percent
100
. . . . . . i ............
80
-.-.
I
0
-.-1- \ 60
'0__ +_-----
40
20
1
rno
3
5
7
Years
9
11
15
13
Fig. 1. Actuarial survival curve for all recipients of heart valve prostheses. Curve includes operative mortality. Five-year survival rate is 86% and 10 year survival rate 75%. Total number followed up at 5 years is 120, at 10 years 22; only seven have been followed up longer than II years, and the drop at 12 years is therefore of questionable significance (large standard error).
prostheses were implanted (Starr size 0 or 1 in 15 patients, and Bjork 17 or 19 mm in 20 children). From the third postoperatiave day, the children received treatment aimed at decreasing the risk of emboli: Those in whom prothrombin time could be regularly checked received warfarin sodium (Coumadin); those living far from major hospitals received aspirin (20 rug/kg/day) and dipyridamole (5 tug] kg/day). Follow-up was done by local hospitals and physicians, whoreturned questionnaires, and by social workers from the Third World organization Terre des Hommes, located in the respective countries, who maintained contact with the patients and reported back at regular intervals. Actuarial survival curves (and event-free percentages) were calculated according to the method of Anderson and associates.I
Results Operative mortality. Four patients died during the operation, and nine within 1 month after the operation, for an early mortality of 4.7%. Most of these patients had end-stage heart failure from rheumatic heart disease.
In survivors, improvement after operation was fast and often spectacular, the children returning to normal activities within 1 or 2 months. Long-term follow-up. Of the 260 survivors,48 (18%)
Table I. Prostheses implanted in 273 children Starr-Edwards Bjork-Shiley S1. Jude Medical Hancock
Mitral
Aortic
Tricuspid
Total
231 1
32 52 7
3 5
266 58 7 ......Q 337
6
patients were lost to follow-up; the remaining patients were observed for a total of 887 patient-years (mean 4.2 years, maximum 15 years). There were 23 late postoperative deaths, 2 months to 12 years after operation. Fig. 1 shows actuarial survival curves for the whole group, and Fig. 2 for mitral, aortic, and mitral plus aortic replacement. Cumulative survival rate is 86% ± 3% at 5 years, and 75% ± 5% at 10 years for the total group (operative mortality included). For isolated mitral prostheses, the figures are 87% ± 3% at 5 years and 82% ± 4% at 10 years, but with no further death to 15 years. For patients with Starr-Edwards mitral prostheses (excluding the seven Hancock and Bjork-Shiley prostheses), survival is slightly better: 89% ± 3% at 5 years, and 83% ± 4% at 10 years. For isolated aortic valve replacement, there was 94% ± 4% survival at 5 years. The sharp drop at 7 years is related to one death in a very small cohort followed, and cannot be considered significant (very large standard error of 26%). In patients with mitral plus aortic valve replacement, the
82
The Journal of Thoracic and Cardiovascular Surgery
EI Makhlouf et al.
Percent 100
e_ ' !"---'
·:::::.... -·c:::::::::: . _·-I-· <, .---- - .
80
-
1"
"'"_:~~\
,, , ,,
60
:=!-J_:=:=:=:= I
-.- - - ...
40 e Mitral
• Aortic
20
" Mitral + Aortic
1
mo
3
5
7
Years
9
11
13
15
Fig. 2. Actuarial survival curves (including operative mortality) given separately for mitral, aortic, and mitral plus aortic valve replacement. Probability of survival for patients with mitral prostheses is 82% at 10 and 15 years, for patients with mitral plus aortic prostheses 77%. For isolated aortic prostheses, the sharp drop occurring between 7 and 8 years is the result of one death in a very small cohort followed, and is therefore of questionable significance (very large standard error).
Table Il, Causes of late deaths Thrombosis, embolism Heart failure Bacterial endocarditis Prosthetic valve detachment Noncardiac Unknown
8 5 2 1 2
..2 23
survival rate at 10 years is 77%. The causes of late death are listed in Table II. Thromboembolic events were the most common cause of late deaths, followed by heart failure.
Complications. Thromboembolic events. There were 24 thromboem-
bolic events (linearized rate 2.7 per 100 patient-years). Clinically significant embolic episodes occurred 18 times; eight accidents were fatal. Thrombotic obliteration of a valve occurred six times, four times in tricuspid prostheses; thus four of seven survivors of tricuspid valve replacement had thrombosis and died. Emboli occurred in the central nervous system in 16 patients, coronary artery in one (with myocardial infarction), and retinal artery in one. Four of the patients with embolic accidents to the central nervous system had significant neurologic sequelae; three had minimal residua. Two patients had more than one embolic episode.
Figs. 3 and 4 show actuarial curves indicating percentage of patients free from thromboembolic events. At 5 years, 88% ± 3% are free of thromboemboli, and at 10 and 15 years 77% ± 6%. None of the patients with an isolated aortic prosthesis had a thromboembolic accident. Of patients with isolated mitral prosthesis, 81% ± 6% are free of thromboemboli at 10 years (80% if Starr-Edwards prostheses are considered exclusively); of patients with mitral plus aortic prostheses, 78% ± 8% are event free. These subgroups show higher event-free percentages than the total group because they do not include patients with tricuspid prosthesis, in whom thrombosis was extremely frequent. Anticoagulants and thromboemboli. Eighty-three children received warfarin anticoagulants on a regular basis. There were seven (8.4%) thromboembolic events in this group; the linearized rate is 2.3 per 100 patientyears. One hundred fifty children received treatment to reduce platelet adhesiveness (aspirin and dipyridamole). Thirteen (8.7%) patients had thromboemboli; the linearized rate is 2.3 per 100 patient-years. Twenty-one patients have stopped taking medication for various reasons, and four (19%) had emboli. The differences between these groups are statistically not significant (by the chi square test), for the latter group (no treatment) because of the small sample size. Two patients had severe hemorrhage: One had multiple hematomas and nose bleeds while taking warfarin,
Volume 93 Number 1 January 1987
Prosthetic heart valve replacement in children
Percent 100 _ . _
·_1I-·___
80
·-t-·-.
83
1-·-·-·-·-1
- - ·<,
60
40
20
3
5
7
Years
9
11
13
15
Fig. 3. Actuarial curves indicating percentage of patients free from thromboembolism (total group). At 5 years, 88% are embolus free, and at 10 years 77%.
. "--._1 . y--.
Percent 100,/"'ll;:::-------- - - - - - - - ~.
80
--.
-·-·-r-·-·"" f 1-·-·-·-·-·-f-·_·-·-·-f I
~.
e-
""
T
-e-e-.
60
• Mitral
40
• Aortic • Mitral + Aortic
20
3
5
7
Years
9
11
13
15
Fig. 4. Actuarial curves indicating percentage of patients free from thromboembolism, given separately for recipients of mitral prostheses, aortic prostheses, and mitral plus aortic valve replacement. None of the patients with aortic valve replacement only had a thromboembolic accident. At 10 years, 81% of patients with mitral prostheses are embolus free, versus 78% of patients with mitral plus aortic prostheses.
and the other had massive gastric hemorrhage while taking aspirin. Both recovered. Endocarditis. There were five cases of bacterial endocarditis, which proved fatal in two patients. One patient died despite two reoperations; the three others received medical treatment only, and recovered. The microorganism is known in three patients: Streptococ-
cus epidermidis, Haemophilus parainfluenzae, and a-hemolytic Streptococcus, respectively. In one patient endocarditis occurred shortly after, and was probably related to, the operation; in another, a dental abscess was found containing the same germ; and in the remaining patients the site of entry was unknown. Valve detachment and degeneration. Four prosthetic
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valves became partially detached. One patient died, having refused reoperation; the other three underwent successful reoperation. Two Hancock prostheses degenerated, calcified, and thrombosed. One patient died, and the other underwent successful reoperation. Discussion Valve replacement in children can be performed with low mortality." However, implanting artificial valves in a young population poses a number of problems: (1) Because of the long life expectancy, durability of the valve is of major concern. (2) Anticoagulant treatment, recommended for all bearers of mechanical valves, may be hazardous in children who are physically very active, and requires regular controls not always easy to obtain in developing countries. (3) "Outgrowing" of a valve is a concern when small-diameter prostheses must be implanted. There is no doubt that bioprostheses should no longer be used in children, because degeneration and calcification occur rapidly in these valve substitutes"; valve survival at 7 years is onlyI8%.7 Mechanical prostheses, on the other hand, especially Starr-Edwards prostheses, have an excellent record of durability9-11 and are virtually indestructible. This is the main reason why we continue to use Starr-Edwards valves in our institution. However, there are valve-related complications, the most important being valve thrombosis and embolism, Fortunately, it appears that thromboembolism is less common in children than in adults with valve prostheses. In adults, about four to six thromboembolic episodes per 100 patient-years are reported for mitral prostheses, the figures being lower for aortic prostheses.10-13 In children, some groups report a very low incidence of thromboemboli: 0.8 to 1.7 per 100 patient-years.s-" In our series, the linearized rate of 2.7 per 100 patient-years is somewhat higher; still, with mitral valve replacement 81% of patients are embolus free at 10 years, a percentage that has not been described in adult patients. No child with aortic valve replacement only had an embolus; this is in striking contrast to the data reported by the Mayo Clinic, where the risk of thromboemboli was higher in children with aortic than with mitral prostheses." Patients with multiple valve replacement have a somewhat higher incidence of thromboemboli; but by far the highest risk of thrombosis is encountered in tricuspid valve replacement (four of seven in our series). Tricuspid valve replacement is therefore avoided in our institution. Anticoagulant therapy is a major problem in children,
Thoracic and Cardiovascular Surgery
especially from Third World countries. Whenever it is evident that regular prothrombin time tests cannot be performed, we prescribe dipyridamole and aspirin as the only treatment. In our large series, we found that these children do not have more thromboemboli than patients given warfarin. However, we do not know how many children receiving warfarin have consistantly optimal levels of prothrombin time. It has been shown that only patients with optimal control are effectively protected from emboli by warfarin"; thus the incidence of emboli may be further reduced in children if constantly efficient anticoagulation is achieved. The fact that only one of our patients had anticoagulant-related hemorrhage may be an indication that many children received suboptimal doses of warfarin. Other complications have been comparatively rare. There were five cases of endocarditis, of which three responded to medical therapy. Valve dehiscence has also been uncommon, and can be treated effectively by reoperation. The problem of "outgrowing" the prosthesis deserves some comment. When very small valve prostheses must be implanted, replacement with a larger one becomes mandatory as the child grows.16,17 Thus far none of our children has required another operation for this reason. Indeed, the left side of the heart was markedly dilated in most patients, and a Starr-Edwards No.2 (or larger) mitral prosthesis could be implanted in the vast majority aged 4 years or older. Of the few children who received No. 1 prostheses, some may require reoperation. One of. these children, operated on at age 2 years, underwent recatheterization 6 years and again 9 years after implantation of a Starr-Edwards No.1 mitral prosthesis;onlya minimal gradient was found. The problem of outgrowing the prosthesis may be more important in our patients with small aortic prostheses, because Bjork 17 and 19 mm valves will become "stenotic" when the children reach adulthood. Replacement of aortic prostheses can be done without major problems." We conclude from this study that valve replacement in children can be done with a low operative mortality and satisfactory late survival; indeed, 10 years after operation, 80% of those who left the hospital are expected to be alive. Thromboembolism is a problem in patients with mitral or multiple valve replacement; however, the complication is less frequent than in adults, even in children receiving no warfarin anticoagulation but only antiplatelet drugs. Tricuspid prostheses havea very high rate of thrombosis and should be avoided whenever possible. Although children with advanced rheumatic heart
Volume 93 Number 1 January 1987
disease benefit enormously from valve replacement, the ultimate solution to this serious problem in Third World countries is eradication of rheumatic fever. REFERENCES
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Anderson RP, Bonchek LI, Grunkemeier GL, Lambert LE, Starr A: The analysis and presentation of surgical results by actuarial methods. J Surg Res 16:224-230, 1974 John S, Bashi VV, Jairaj PS, Muralidharan S, Ravikumar E, Sathyamoorthy I, Babuthaman C, Krishnaswamy S, Cherian G, Sukumar IP: Mitral valve replacement in the young patient with rheumatic heart disease. J THORAC CARDIOVASC SURG 86:209-216, 1983 Berg T, Keck EW: Mitral- und Aortenklappenersatz im KindesaIter. Z Kardiol 73: 173-180, 1984 Friedli B, Friedli GM, Ben Ismail M, Rouge JC, Hahn Ch, Faidutti B: Remplacement valvulaire chez I'enfant. Resultats et suites eloigneeschez 171 operes, Schweiz Med Wochenschr 111: I044-1048, 1981 Thandroyen FT, Witthon IN, Pirie D, Rogers MA, Mitha AS: Severe calcification of glutaraldehyde preserved porcine xenografts in children. Am J Cardiol 45:690-696 1980 ' Silver MM, Pollock J, Silver MD, Williams WG, Trusler GA: Calcification in porcine xenograft valves in children. Am J Cardiol 45:685-689, 1980 Antunes MJ: Bioprosthetic valve replacement in children. Long term follow-up of 135 isolated mitral valve implantations. Eur Heart J 5:913-918, 1984 Attie F, Kuri J, Zanoniani C, Renteria V, Buendia A, Obseyevitz J, Lopez-Soriano F, Garcia-Cornejo M, Martinez-Rios MA: Mitral valve replacement in children with rheumatic heart disease. Circulation 64:812-817,1981 McGoon M, Fuster V, McGoon DC, Pumphrey CW, Pluth JR, Elveback LR: Aortic and mitral valve incompe-
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tence. Long-term follow-up of patients treated with the Starr-Edwards prostheses. J Am Coli Cardiol 3:930-938, 1984 10 Miller DC, Oyer PE, Mitchell RS, Stinson EB, Jamieson SW, Baldwin JC, Shumway NE: Performance characteristics of the Starr-Edwards Model 1260 aortic valve prosthesis beyond ten years. J THORAC CARDIOVASC SURG 88:193-207,1984 11 Miller DC, Oyer PE, Stinson EB, Reitz BA, Jamieson SW, Baumgartner WA, Mitchell RS, Shumway NE: Ten to fifteen year reassessment of the performance characteristics of the Starr-Edwards Model 6120 mitral valve prosthesis. J THoRAc CARDIOVASC SURG 85: 1-20, 1983 12 Edmunds LH: Thromboembolic complications of current cardiac valvular prostheses. Ann Thorac Surg 34:96-106, 1982 13 Fuster V, Pumphrey CW, McGoon MD, Chesebro JH, Pluth JR, McGoon DC: Systemic thromboembolism in mitral and aortic Starr-Edwards prostheses. Circulation 66:Suppl 1:157-161, 1982 14 Schaff HV, Danielson GK, Di Donato RM, Puga FJ, Mair DD, McGoon DC: Late results after Starr-Edwards valve replacement in children. J THoRAc CARDIOVASC SURG 88:583-589, 1984 15 Friedli B, Aerichide N, Grondin P, Campeau L: Thromboembolic complications of heart valve prostheses. Am -. Heart J 81:701-708,1971 16 Williams WG, Pollock JC, Geiss DM, Trusler GA, Fowler RS: Experience with aortic and mitral valve replacement in children. J THoRAc CARDIOVASC SURG 81:326-333, 1981 17 Friedman S, Edmunds LH Jr, Cuaso CC: Long term mitral valve replacement in young children. Influence of somatic growth on prosthetic valve adequacy. Circulation 57:981-986, 1978