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Heart valve replacement with the Ionescu-Shiley pericardial xenograft
Heart valve replacement with the Ionescu-Shiley pericardial xenograft Between March, 1971, and September, 1975, glutaraldehyde-stabilized pericardial xenografts were used for single valve replacement in 212 patients (142 aortic, 67 mitral, and three tricuspid). The 195 operative survivors were observed for a total of 5,926 months over a period of 6 to 61 months (mean 30). Actuarial analysis of late results indicates an expected survival rate at 5 years of 92.3 per cent for patients with aortic and 91.1 per cent for patients with mitral valve replacement. The rate of systemic embolism has been 0.62 episodes per 100 patient years for the aortic and 2.48 episodes per 100 patient years for the mitral group in the absence of anticoagulant treatment. All six emboli occurred early postoperatively, were trivial or mild, and left no sequelae. Symptomatically, 96.7 per cent of patients are now in Class I and 3.3 per cent in Class II (N.Y.H.A.). Maintenance of structural and functional integrity of the glutaraldehyde-stabilized pericardial xenograft was demonstrated by histologk and hemodynamic investigations. Catheterization showed substantial circulatory improvement in both patients with aortic and those with mitral replacement. The transaortic gradients were negligible (8 mm. Hg at rest and 17.5 mm. Hg during exercise). The available evidence indicates that results of valve replacement with pericardial xenografts, over this period of follow-up, compare very favorably with those obtained with other available prostheses and tissue valves.
Marian I. Ionescu, M.D. (by invitation), Anand P. Tandon, M.D. (by invitation), David A. S. Mary, M.D. (by invitation), and Abdelfettah Abid, M.D. (by invitation), Leeds, England Sponsored by Dwight C. McGoon, M.D., Rochester, Minn.
O ince the beginning of heart valve replacement there have been two periods of technical development. During the first period valve replacement became established as a safe procedure. The second period has been marked by attempts to approach perfection. The clothcovered prostheses have reduced the rate of thromboembolism but have created new mechanical and hemodynamic problems.4 Although the tilting disc valves represent a step forward in valve hydraulic function, they still require prothrombin depressants.3 In the development of tissue valves an important advance has been made by the introduction of permanent tissue tanning with glutaraldehyde.7 The use of the porcine aortic valve has proved the veracity of this concept.9' 29 From the Department of Cardiothoracic Surgery, The General Infirmary, Leeds, England. Read at the Fifty-sixth Annual Meeting of The American Association for Thoracic Surgery, Los Angeles, Calif., April 23, 24, and 25, 1976. Address for reprints: Marian I. Ionescu, M.D., Department of Cardiothoracic Surgery, The General Infirmary, Great George Street, Leeds LSI 3EX, England.
In an attempt to reach the three primary goals of an ideal valve substitute, namely, freedom from thromboembolism without anticoagulation, near-normal hydraulic performance, and maintenance of long-term structural and functional integrity,17 we18 introduced in 1971 the glutaraldehyde-stabilized pericardial xenograft heart valve. This report presents our experience with pericardial xenografts inserted in 212 patients since March, 1971. Clinical material and methods During the period from March, 1971, through September, 1975, pericardial xenografts were inserted in 212 patients as single valve replacements. There were 142 patients with aortic, 67 with mitral, and 3 with tricuspid replacement. The age and sex incidence as well as the type of valve lesions are shown in Tables I and II. The mean ages were 48.7 for the aortic and 44.7 years for the mitral valve replacement group. In the aortic group there were 28 patients with additional mitral valve lesions, in the mitral group 34 patients had aortic or tricuspid lesions or both, and one patient from 31
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Table I. Age and sex incidence of 212 patients
Table IV. Preoperative clinical details in 212 patients
Age (yr.) Valve
11-20 21-30
Aortic Male Female Mitral Male Female Tricuspid Male Female
31-40
41-50
51-60
61-70
7 5
18 4
24 8
36 13
19 6
106 36
_
4 13
14 17
4 10
2 1
25 42
2
-
-
-
22 19
38 25
40 23
21 7
1 1
Totals Male Female
8 6
1 2 132 80
Table II. Type of valve lesion in 212 patients Aortic Valve lesion
M
F
Stenosis 36 12 Regurgitation 3 1 1 2 Mixed disease 34 10 Malfunction of 5 2 previous valve substitute
Total
Mitral M
F
Tricuspid
Total
48(47) 6 8 14(10) 43 6 5 1 1 44 (38) 13 27 40 (22) 7 - 2 2
M
F
Total
1 1 2 1 1 - - -
Legend: M, Male. F, Female. Figures in parentheses denote number of patients with valve calcification.
Table III. Etiology of valve lesion in 212 patients Aortic Rheumatic Ruptured chordae tendineae Indeterminate Congenital Endocarditis Syphilis Rheumatoid arthritis Marfan's disease Malfunction of previous valve substitute Traumatic Totals
61
-
29 23 7 3 4 8 7
Mitral
Tricuspid
60 3
2
-
1 1
-
2
Aortic
Total
-
-
-
1
142
67
3
the tricuspid group had mitral incompetence. These additional valve lesions varied from trivial to severe. The cause of the valve lesions is shown in Table III. Patients were evaluated on the basis of the New York Heart Association (N.Y.H.A.) classification, and their condition prior to operation is outlined in Table IV.
Mitral
N.Y.H.A. Class I 11 III IV
6 72 61 3
13 42 12
Syncope Angina Myocardial infarction Systemic embolism Hypertension Chronic bronchitis Epilepsy
35 78 2 5 6 8 1
3 6 1 10 2 9 5
Sinus rhythm Atrial fibrillation Complete heart block
130 8 4
17 50
Tricuspid
-
-
Table V. Concomitant surgical procedures performed at the time of valve replacement in 212 patients Surgical procedure Aorta-coronary SVBG Removal of left atrial thrombi Closure of left-to-right shunt (PDA, ASD, VSD) Wedge resection of left ventricular outflow tract Ascending aorta replacement Mitral commissurotomy Mitral annuloplasty Decalcification of mitral valve Tricuspid annuloplasty Implantation of permanent pacemaker Totals
Aortic
Mitral
11
1 7
-
5
-
39
-
9 5 14 17
_ -
-
4 104 (74)
Tricuspid
6 2
16(15)
1 (1)
Legend: SVBG, Saphenous vein bypass graft. PDA, Patent ductus arteriosus. ASD, Atrial septat defect. VSD, Ventricular septal defect. Figures in parentheses denote number of patients with concomitant surgical procedures.
The duration of the disability ranged between 2 weeks and 8 years. In the aortic group, 2 patients had had previous open aortic valvotomy and one had had pericardiectomy. In the mitral group, 21 patients had had one or two previous closed commissurotomies and one patient had had mitral annuloplasty. At the time of valve replacement, 121 additional surgical procedures were performed in 90 patients as shown in Table V. Description of the pericardial xenograft. The pericardial xenograft used throughout this series consisted of bovine pericardium mounted as a three-cusp
Volume 73 Number 1 January, 1977
Valve replacement with pericardial xenograft
33
Table VI. Details of pericardial xenograft size, type of suturing, and perfusion duration in 212 patients Implantation diameter of xenograft (mm.) Valve
19
21
23
25
27
29
Aortic Mitral Tricuspid
1
36
57
-
36 3 -
6 52 2
12 1
-
-
Perfusion* duration (min.)
Type of sutures used
_
Interrupted
Continuous
129 5
1 46
-
Mixed
Range
12 16 3
47-300 27-186 22-65
Mean 98 56 40
♦Includes total perfusion duration required for valve replacement and concomitant surgical procedures.
valve onto a Dacron-covered titanium support frame.2 The majority of patients received valves constructed in our own laboratory. Only minor changes have been made in the configuration of the sewing rim and in the quality and concentration of the solutions used during the past 5 years. For the past few months the xenografts have been manufactured by Shiley Laboratories.* Although essentially similar to the valves initially used, the Ionescu-Shiley pericardial xenografts are now manufactured by standardized techniques, the tissue being subjected to an improved treatment of stabilization with "purified glutaraldehyde."34 The lightweight titanium frame is covered with thin Dacron velour fabric to facilitate encapsulation without increasing the bulk of the valve. The sewing rim, which contains porous Teflon fabric, has the same configuration for all valve sizes and permits insertion of the valve in both the aortic and atrioventricular positions (either sub- or supra-annular). The pericardium is obtained from calves 6 to 18 months old. From the time of collection, sterile procedures are observed during the whole process of valve manufacture. Strips of pericardium of even thickness are selected, mechanically cleaned, and washed for 3 hours in Hanks solution. The stabilization and fixation of the tissue is performed with 0.5 per cent purified glutaraldehyde buffered to pH 7.4 with 0.067M phosphate at 4° C. for 2 weeks. The native structure of the pericardial tissue is permanently stabilized by the formation of inter- and intramolecular covalent bonds between the amino groups of lysine and hydroxylysine residues (present in collagen, elastin, glycoproteins, and proteoglycans) and various forms of glutaraldehyde. The total tissue antigenicity is significantly attenuated by this chemical immobilization and stabilization process with purified glutaraldehyde. The tissue cross-link density (evaluated by temperature shrinkage techniques) is optimal when 0.5 per cent *Shiley Laboratories, Inc., Santa Ana, Calif.
purified glutaraldehyde is used as the chemical stabilizing agent. This concentration ensures complete tissue sterility. Following the stabilization with purified glutaraldehyde, the pericardium is stored in 4 per cent formaldehyde buffered to pH 5.4 with 0.2M acetate. This treatment produces optimal tissue flexibility and maintains its sterility during storage. The stabilized pericardium is mounted on the outer aspect of the frame in order to maintain intact the central opening of the valve, which is the inside diameter of the support frame. One single strip of pericardium is used for the construction of all three cusps. As a result of this technique, as well as the thinness of the tissue and the geometry of the valve and sewing rim, the orifice area-annulus diameter ratio is optimal even for the very small size aortic xenografts. Operative technique. All valve replacements were performed through a median sternotomy by use of euthermic conventional cardiopulmonary bypass. For aortic valve replacement, 122 patients had left coronary perfusion and 17 patients both left and right coronary perfusion and the heart was allowed to contract. In 3 patients hypothermic arrest was used. For mitral replacement, intermittent hypoxia with local hypothermia was the routine procedure. The size of the xenografts used, the type of suturing for implantation, and the duration of cardiopulmonary bypass are shown in Table VI. Results The definition of terms used is as reported in previous publications.19, 28 Standard statistical formulas were used for the analysis of results. Early death. Seventeen patients (8.1 per cent) died between the first and forty-fifth day following operation. There were 11 deaths (7.7 per cent) in the aortic and 6 (8.9 per cent) in the mitral valve replacement group. The causes of early deaths are shown in Table VII. Follow-up. All hospital survivors, with the exception
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3 4 Ionescu et al.
- l - S PERCAROAL XENOGRAFT-
-l-SPERCARCXAI. XENOGRAFT-
%
MITRAL REPLACEMENT
AORTIC REPLACEMENT
100
,^_
90
100
SURVIVAL RATE (2)
(4)
92.37.
(1)
SURVIVAL RATE
* - N ^
90
(3)
9t17.
(1)
80
80 7 late deaths (5.3%)
4 late deaths (6.55%)
2 SBE.
1 S.BE
1 heart falure
2 myocardial infarction
J*
»
1 mesenteric thrombosis
1 malgnancy 1 sudden
1 dissection descending aorta 1 cusp tear 0
64
96
130
®'
2
39
3
9
46
61
34
®C
4
YEARS FOLLOW-UP
2
»
19
4
3
2
5
YEARS FOLLOW-UP
Fig. 1. Actuarial representation of expected survival rate for patients with aortic and mitral pericardial xenograft valve replacement. The number and causes of late deaths are shown for both the aortic and mitral groups. S.B.E., Subacute bacterial endocarditis.
- l - S PERICARDIAL XENOGRAFT-
- I-S PERICARDIAL XENOGRAFT-
%
AORTIC REPLACEMENT
%
100
98.3% 962% 94.4% 92.3%
100
MITRAL REPLACEMENT
%>-.
80
—
90
—
Survival Rate
—
T. Embolism
■
SBE.
—
Re-Op
"—
D. Murmur
80
®'
1
(96)
Survival Rate
*' 2
(64)
3
(39)
4
YEARS FOLLOW-UP
SMurmur S.B.E.
0 (130)
92.2%
91.1 V. 90.1%
Free of:
Free of: —
96.27,
x ^ ^- « ^
90 852%
98.1 %
\^C
©°
■—
T. Embolism
—
Re-Op
61
46
34
2
19
3
8
4
2
5
YEARS FOLLOW-UP
Fig. 2. Actuarial analysis of results following aortic and mitral pericardial xenograft valve replacement. The data are expressed as per cent expected survival rate and individual event-free curves for complications.
of one who is living abroad, have been examined by one of the authors at 6 month intervals for the entire period of follow-up. In addition to physical examination, chest radiograms and electrocardiograms were obtained at each visit. Other laboratory investigations including hemodynamic and angiographic studies were performed in a series of patients. There were 194 patients observed over a period of 6 to 61 months for a total of 5,926 months (mean 30). In the aortic group, 130 patients were observed for 3,852 months (mean 29.4); in the mitral group, 61 patients
were followed for 1,931 months (mean 31.7); and the 3 patients with tricuspid valve replacement were followed for 143 months (mean 47.3). Late death. There were 11 late deaths (5.7 per cent), 7 (5.3 per cent) with aortic and 4 (6.5 per cent) with mitral valve replacement. The causes of death are outlined in Table VIII. In 4 patients the death was related to the valve (three aortic and one mitral) and was the consequence of infective endocarditis in 3 and of a torn valve cusp in the aortic position in one patient. The actuarial analysis for survival rate in both the
Volume 73 Number 1 January, 1977
Valve replacement with pericardial xenograft
Table VII. Causes of early death in 212 patients Cause
Aortic
Cardiac Pump failure Ventricular dysrhythmia Myocardial infarction Endocarditis Noncardiac Mediastinitis Gastrointestinal hemorrhage Cerebral infarction Totals
Mitral
1 11 (7.7%)
6 (8.9%)
Table VIII. Details of late deaths in 195 hospital survivors Age (yr.)
Sex
Aortic (7 deaths M 51 M 64 M 37 M 55
Time postop. (mo.) 6 9 9 10
58
M
17
51 38
M M
24 32
Mitral (4 deaths F 58
44 46 69
F F M
8
11 11 31
Cause of death Mesenteric vein thrombosis Myocardial infarction Endocarditis, heart failure Endocarditis, reop., triple valve replacement, heart failure Acute dissection of descending aorta Myocardial infarction Cusp tear, hemolysis (three previous valve replacements), right ventricular laceration at reop. Endocarditis, reop, valve replacement, myocardial infarction Heart failure, no autopsy Sudden death, no autopsy Malignant pleural effusion, no atuopsy
Legend: F, Female. M, Male.
aortic and mitral groups is shown in Fig. 1. The predicted survival rate for patients with aortic replacement is 95.5 per cent at one year and 92.3 per cent at 3 and 5 years. For patients with mitral replacement, the predicted figures are 94.1 per cent at one year and 91.1 per cent at 3 and 6 years. Thromboembolism. Routine anticoagulant treatment was not used in this series even during the early postoperative period. All embolic episodes occurred early postoperatively, were trivial or mild, and left no sequelae. There were six instances of emboli in the
35
Table IX. Early diastolic murmurs in patients with pericardial xenograft replacement of aortic valve Diastolic murmurs Early Late Total
13(9.1%) 2(1.4%) 15(10.5%)
Valve lesion Heavily calcified aortic valve and annulus Gross dilatation of aortic annulus Associated mitral valve lesion Complex congenital anomaly of aortic root Previous aortic valve replacement
10 2 5 2 2
Clinical course Duration of follow-up with murmurs (mo.) 6-54 (17.6) No. of patients in Class I (N.Y.H.A.) 15 No change in CTR and left ventricular voltage Treatment* None 7 Hematinic agents 2 Diuretic drugs 4 Antihypertensive drugs 2 Surgical closure of perivalvular leak 1 Legend: CTR, Cardiothoracic ratio. *Perivalvular leak seen and "repaired" at initial operation in 7 patients.
entire series (1.2 episodes per 100 patient years). Valve thrombosis has not been encountered. In the aortic replacement group, 2 patients developed transient visual field defects on the fourth and sixteenth postoperative days, immediately following successful cardioversion for atrial fibrillation. One of these patients had mitral comissurotomy at the time of valve replacement. For the aortic group, the incidence of thromboembolism was 0.62 episodes per 100 patient years. Four patients in the mitral group had mild and transient pareses 3, 17, 30, and 42 days following the operation. All 4 patients were in atrial fibrillation and had a grossly enlarged left atrium. For the mitral replacement group, the incidence of thromboembolism was 2.48 episodes per 100 patient years. Actuarial analysis predicts that 98.3 per cent of patients with aortic and 92.2 per cent of patients with mitral replacement will be free of thromboembolism after 5 and 6 years, respectively (Fig. 2). Infective endocarditis. Endocarditis developed in 5 patients (2.3 per cent) in this series. There were 3 such patients in the aortic group (2.1 per cent). In one (with additional mitral annuloplasty) the infection occurred 4 months postoperatively. Antibiotic treatment was effective but reoperation was required 6 months later for heart failure. The patient died of heart failure shortly after triple valve replacement. In the second patient
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3 6 Ionescu et al.
AORTIC
n123
"■EW H
i.rr]/ PRE-OP
□
POST-OP
MITRAL
n55
-B|B III
36 ' /
I 0 I
"□' B PRE-OP
POST-OP
Fig. 3. Diagrammatic presentation of the pre- and postoperative N.Y.H.A. functional classification of 123 patients with aortic and 55 patients with mitral pericardial xenograft valve replacement. (with concomitant replacement of the ascending aorta) endocarditis developed 8 months postoperatively, following repeated dental extractions without antibiotic cover. The patient died shortly after hospital admission. In the third patient, endocarditis developed 21 months after valve replacement following respiratory tract infection. The valve was successfully replaced with another pericardial xenograft 26 months after the initial operation. The patient continues to be well. Endocarditis developed in 2 patients who had mitral valve replacement (2.9 per cent). The infections occurred one and 5 months postoperatively. Both had reoperation and valve replacement, but both died, the first of heart failure one month after reoperation and the second of myocardial infarction 3 months following reoperation. Represented actuarially, 96.2 per cent of patients in both the aortic and mitral groups are predicted to be free of infection 5 and 6 years postoperatively, respectively (Fig. 2). Reoperation. Eight patients (3.7 per cent) in the entire series underwent reoperation, 4 of them because of endocarditis or its sequelae as already described. Of the 4 remaining patients, 2 had aortic and 2 mitral replacement. One patient had a perivalvular leak which was successfully obliterated 7 months following aortic valve replacement. One other patient with aortic replacement developed a diastolic murmur and hemolysis 26 months postoperatively. During reoperation (at 32 months), irreparable laceration of the heart occurred owing to adhesions from three previous valve replacements. One cusp of the xenograft was vertically torn
for 4 mm. from the free margin downward. Except for this, the valve was essentially normal. Two patients from the mitral valve replacement group underwent successful reoperation and prosthetic valve replacement 13 and 31 months following xenograft insertion. In both patients one cusp of the valve had become disinserted from the support frame. Otherwise, the cusps looked normal. Prior to planned reoperation, the 2 patients had medical treatment for their left ventricular failure for 6 and 10 weeks, respectively. Of the 4 patients reoperated upon for mechanical defects related to the valves, 3 are alive and asymptomatic. The predicted event-free curve for reoperation is shown in Fig. 2. Murmurs. Early diastolic murmurs were heard in 15 patients (10.5 per cent) in the aortic group. In 13 (9.1 per cent) they occurred in the early postoperative period, whereas in 2 (1.4 per cent) they were noted 31 and 36 months following operation. Table IX outlines clinical and operative details concerning the patients with diastolic murmurs. In 7 patients perivalvular leaks were detected at the time of initial valve replacement and attempts were made to obliterate them. One patient had the perivalvular leak successfully closed at reoperation 7 months following xenograft insertion. All 15 patients are now in Class I (N.Y.H.A.) with no clinical deterioration or statistically significant changes in cardiothoracic ratio and electrocardiogram at a follow-up of 6 to 54 months (mean 17.6). In the mitral replacement group, there were 4 patients in whom apical systolic murmurs (three midsystolic and one pansystolic) were heard from the early postoperative period. Left ventricular angiograms performed in 3 of them did not show any regurgitation. The fourth patient died of a malignant pleural effusion 31 months postoperatively, before angiography could be performed. Thus the incidence of regurgitant murmurs in the mitral group is 1.4 per cent. The predicted event-free curve for murmurs is shown in Fig. 2. Clinical condition. Pre- and late postoperative N.Y.H.A. classifications are diagrammed in Fig. 3. Preoperatively, the majority of patients were in Classes II and III. All except 6 patients are now in Class I. Of these 6 subjects, 4 have chronic bronchitis and 2 have developed ischemic heart disease since the operation. Electrocardiographic and radiologic changes. Preoperatively, 112 patients from the aortic and 16 from the mitral replacement group were in sinus rhythm, as compared with 109 and 15, respectively, at the most recent evaluation.
Volume 73 Number 1 January, 1977
37
Valve replacement with pericardial xenograft
Table X. Preoperative and latest postoperative cardiothoracic ratio and left ventricular voltage in 180 long-term survivors with pericardial xenograft replacement of aortic & mitral valves CTR (%) Valve lesion Aortic Stenosis Incompetence Mixed disease All patients Mitral Stenosis Incompetence Mixed disease All patients
LV voltage
Preop.
Postop.
Postop.
Preop.
49.8 55.4 55.1 53.3
± ± ± ±
0.7 0.7 1.3 0.6
47.6 49.4 51.0 49.2
± ± ± ±
0.7* 0.6* 1.1* 0.5*
49.4 53.7 50.7 51.2
± ± ± ±
2.2 2.1 1.9 1.2
33.1 42.7 34.3 36.4
55.3 56.6 57.7 56.8
± ± ± ±
2.9 1.8 1.3 1.0
52.4 51.0 53.7 52.9
± ± ± ±
2.6 1.7f 1.3* 1.0*
26.7 46.7 33.8 35.0
± ± ± ±
4.5 3.3 1.9 1.7
32.7 ± 4.4 36.2 ± 3.4$ 31.9 ± 1.9
± ± ± ±
1.6* 1.9* 1.8* 1.1*
32.8 ± 1.5
Legend: Results are expressed as mean : standard error of the mean. CTR, Cardiothoracic ratio. LV, Left ventricular. ♦Highly significant (p < 0.001). tSignificant (p < 0.01). JHighly significant (p < 0.005).
Table XI. Hemodynamic data from the pre- and second postoperative investigation of patients with pericardial xenograft valve replacement Mitral
Aortic Variable Mean pulmonary wedge pressure (mm. Hg) Mean pulmonary artery pressure (mm. Hg) Cardiac index (L./min./sq. M.)
Time of study Preop. Postop. Preop. Postop. Preop. Postop.
Ejection systolic gradient (mm. Hg) Mean diastolic gradient (mm. Hg) Calculated xenograft surface area (sq. cm.) No. of patients Average time of postop. investigation (mo.) Xenograft implantation diameter
Rest 18.7 8.3 35.5 15.3 2.9 3.1 8.0
± 5.7 ±0.6 ± 9.5 ± 0.8 ± 0.1 ± 0.2 ± 0.6
1.6 ± 0.1
Exercise 25.3 18.7 50.2 27.7 4.0 4.4 17.5
± ± ± ± ± ± ±
6.5 2.0 11.7 2.6 0.6 0.3 0.1
2.1 ± 0.1
6 45 4 patients, 23 mm. 2 patients, 25 mm.
Exercise
Rest 19.5 12.7 28.1 21.8 1.9 2.3
± ± ± ± ± ±
1.5 0.6 1.7 1.2 0.1 0.1
6.2 ± 0.8 2.1 ± 0.1
39.8 29.0 59.5 39.4 3.4 3.8
± ± ± ± ± ±
4.7 1.9 7.6 2.0 0.2 0.2
15.8 ± 1.6 2.4 ± 0.1
13 47 10 patients, 27 mm. 3 patients, 29 mm.
Legend: Results are expressed as mean ± standard error of the mean.
As shown in Table X, there was a statistically significant reduction in the mean left ventricular voltage in all patients following aortic valve replacement and in those patients with preoperative pure mitral regurgitation. There was also statistically significant reduction in cardiothoracic ratio in all patients following either aortic or mitral valve replacement. Radiologically, there was no evidence of pericardial xenograft calcification during the period of follow-up. Hemodynamic investigations. Hemodynamic studies at rest and during exercise were performed in 30 patients with either aortic or mitral replacement. The
data from preoperative investigations were compared with those obtained at two separate postoperative studies performed at mean intervals of 10 and 45 months for aortic valve replacement and 14 and 47 months for mitral replacement. The detailed results of this investigation are published separately. At both the first and the second postoperative studies, the majority of patients with pericardial xenografts in the aortic or mitral positions exhibited normal resting pulmonary wedge, pulmonary artery, and left ventricular end-diastolic pressures. Negligible ejection systolic gradients were recorded across the aortic xenografts (8 mm. Hg at rest and 17.5 mm. Hg during exercise) at the second
The Journal of Thoracic and Cardiovascular Surgery
3 8 lonescu et al.
Fig. 4. Comparison between a pericardial xenograft (left) and a porcine aortic valve (right) seen from their outflow aspect. Both valves are frame mounted and both have an implantation diameter of 23 mm. A, The configuration of the valves. B, The difference in effective functional opening when the valve is tested in a pulse simulator at a flow rate of 3 L. per minute and at physiological pressures. postoperative study. There was no significant change in the gradients between the two investigations. The calculated effective xenograft surface area was 1.6 and 2.1 sq. cm. for aortic and 2.1 and 2.4 sq. cm. for mitral valves at rest and during exercise, respectively. The mean diastolic gradients across the mitral xenografts were 6.2 mm. Hg at rest and 15.8 mm. Hg during exercise. There was a significant reduction in pulmonary vascular resistance in patients with mitral replacement at both postoperative studies. Data from the pre- and the second postoperative hemodynamic investigations are given in Table XI. The competence of pericardial xenografts in both the aortic and mitral positions was confirmed by angiograms performed at the second postoperative study. Hemolysis. In patients without murmurs there was no clinical or laboratory evidence of intravascular hemolysis. The results of a specific laboratory investigation are published separately. Pathology. Ten pericardial xenografts were recovered at reoperation or autopsy, 6 to 32 months following insertion. One valve removed from the aortic position 32 months postoperative had a 4 mm. vertical tear in a cusp, near the commissure. Two valves were removed from the mitral position 13 and 31 months fol-
lowing operation. Both had one cusp detached from the support frame. With the exception of the mechanical lesions, these three valves were grossly intact. Three other valves (one mitral and two aortic) were affected by endocarditis. The remaining xenografts were essentially normal. The sewing rim and exposed Dacron surfaces were covered with a thin, glistening layer of fibrous tissue in continuity with the endocardium. Microscopic examination showed that the original histologic components of the pericardium had undergone little, if any, change when compared with unimplanted specimens. There was neither evidence of immune or inflammatory reaction nor of tissue ingrowths on the surface or in the substance of the cusps. Tricuspid valve replacement. There were no early or late deaths and no complications among the 3 patients with tricuspid valve replacement. By clinical criteria, the three pericardial xenografts are competent and functioning satisfactorily. The patients are in Class I (N.Y.H.A.). Discussion The detailed analysis of results obtained over a period of 5 years with the pericardial xenograft in both aortic and mitral positions indicates that over this
Volume 73 Number 1 January, 1977
period of follow-up the three primary goals for which this valve was created have been attained and that no additional, unexpected complications have been encountered. The early mortality rate of 8.1 per cent in the present series is similar to results reported with various other types of valve substitutes.4' 24' 32 The most important single determinant of the quality of a heart valve substitute is the record of patient survival. In this series the actuarial survival rate 5 years following operation (92.3 per cent for aortic and 91.1 per cent for mitral replacement) compares very favorably with published reports concerned with the use of both prostheses4' Ilp 21 and tissue valves.1* 6> 32' 36 There were 4 valve-related deaths in the entire series, and in 3 of them infection was the primary cause. Low thrombogenicity in the absence of anticoagulant treatment is one of the advantage of tissue valves. In the present series, prothrombin depressants were not used at any time following operation. The embolic incidence of 1.2 episodes per 100 patient years for the entire series (0.62 for aortic and 2.48 for mitral replacement) compares very favorably with that encountered following the use of prosthetic valves.13, 24, 26 Furthermore, the embolic rate in the present series is similar to that reported in patients having valve replacement with porcine xenografts, whether or not associated with early postoperative anticoagulant treatment.6' 8 ' 9 ' 32 - 36 An analysis of the emboli which occurred in this series during the 5 years preceding the operation showed an incidence of 2.4 episodes per 100 patient years (1.3 for aortic and 5 for mitral valve disease). This is clearly double the postoperative incidence. The embolic rate in the present series is similar to the incidence observed after mitral valvuloplasty.10'30 Because all emboli occurred in our patients within the first 6 postoperative weeks, it is conceivable that the present rate of embolism could be further reduced by using anticoagulants during this short period of time, especially in patients with enlarged and fibrillating atria. Thrombosis of the valve, which has been described with prostheses4' u and other tissue valves, 14,23 has not been encountered in the present series. The advantage of a low embolic rate and the absence of valve thrombosis without the use of prothrombin depressants becomes even more significant when considering the hazards of long-term anticoagulant therapy.16, 22 There were five episodes of infective endocarditis in this series. The infection developed early in 3 patients (1.4 per cent) and late postoperatively in 2 (one per cent). The early occurrence is considered to be related
Valve replacement with pericardial xenograft
39
to contamination during the surgical procedure or to obvious infections in noncardiac areas during the early postoperative period. Since 1972, we have not encountered any instances of infective endocarditis early postoperatively in our entire open-heart program. This data coincides with a complete change in bacteriologic monitoring of the patients and in the prophylactic administration of antibiotics.12 Both cases of endocarditis of late occurrence were attributed to untreated infective processes (dental manipulation and respiratory infection). In general, infective endocarditis is not related to a particular type of valve substitute. Its incidence in this series is similar to that in other published reports.21' 2 5 ' 3 5 The incidence of early diastolic murmurs (10.5 per cent) in the present series of patients with aortic valve replacement is relatively high but similar to some reports concerning both prosthetic3' 24' 31 and tissue valve replacements.1' 8 ' 32 In all 15 patients with diastolic murmurs the local anatomic circumstances were conducive to the occurrence of peri valvular leaks. In 7 of these patients, perivalvular leaks were detected before the conclusion of the operation and efforts were made to obliterate them. A perivalvular leak was indeed the cause of the murmur in the only patient who required reoperation. Until the final shape and size of the pericardial xenograft sewing rim were established, changes were made; the early models of uncushioned rims might have contributed to the occurrence of leaks. All of the patients with diastolic murmurs are asymptomatic 6 to 54 months from the appearance of the murmur. The hemodynamic stress for tissue valves is greater in the mitral area,20 and in this series there was only one patient who had an indication of mitral regurgitation. The previously mentioned evidence led us to believe that the early diastolic murmurs in this series were caused by perivalvular leaks. The pericardial xenograft satisfactorily relieves the hemodynamic abnormalities of valvular heart disease. This fact has been demonstrated by the clinical results and by cardiac catheterization. There is only one published report concerning hemodynamic data in patients with porcine valves in the aortic position, and the transaortic gradients measured in 3 of those patients at rest were, 15, 15, and 35 mm. Hg.33 In the present series the aortic gradients were negligible (5.7 to 9.5 mm. Hg at rest and 17 to 17.5 mm. Hg during exercise). This is due to the very large central opening of the pericardial xenograft and to its optimal orifice area-annulus diameter ratio when compared with porcine aortic valves (Fig. 4). This
40
The Journal of Thoracic and Cardiovascular Surgery
lonescu et al.
quality of the pericardial xenograft makes it a very useful aortic valve substitute for patients with a small aortic annulus. The hemodynamic data obtained in patients with pericardial xenografts in the mitral area compare favorably with results obtained following mitral valve replacement with prostheses 5 and porcine valves. 1 5 , 23, 27, 29 Sequential hemodynamic studies have demonstrated that the circulatory improvement obtained following operation both after aortic and after mitral valve replacement was maintained for at least 47 and 45 months, respectively. The mechanical dysfunction of pericardal xenografts in this series (1.4 per cent) was due to technical faults in the construction of the valves and not to degenerative changes of the pericardial tissue. In the aortic position, only one valve (0.7 per cent) developed a cusp tear. The resulting aortic incompetence was clinically and angiographically insignificant and did not progress over a period of 6 months. Reoperation was required because of hemolysis. From the mitral replacement group, in two valves (2.9 per cent) a cusp became disinserted from the support frame. Planned reoperation was successfully performed in both cases. Such mechanical problems should be eliminated by careful, standardized manufacture of the pericardial xenograft in a specialized laboratory. Five years' experience with heart valve replacement with the pericardial xenograft has shown, in both the aortic and mitral positions, excellent long-term clinical results. The embolic rate was very low in the absence of anticoagulant treatment. The superior hydraulic performance of this valve, especially in small aortic sizes, represents an additional advantage. Very few valve-related complications developed, and the maintenace of structural and functional integrity of the valve was demonstrated by histologic and hemodynamic investigations. Available evidence indicates that the long-term integrity and durability of glutaraldehyde-stabilized tissue is satisfactory. The very encouraging results obtained with the pericardial xenograft fully justify its wider and continued clinical use and evaluation. Addendum Since this paper was submitted, 12 patients with aortic valve replacement from the group of 15 patients with early diastolic murmurs had aortic root angiography. This investigation clearly demonstrated the presence of perivalvular leak in all 12 patients, confirming the clinical impression.
1 2 3
4
5
6
7
8
9
10
11
REFERENCES Barratt-Boyes, B. G.: Discussion of Karp et al.24 Bartek, I. T., Holden, M. P., and lonescu, M. I.: Frame-Mounted Tissue Heart Valves: Technique of Construction, Thorax 29: 51, 1974. Bjork, V. O., Henze, A., and Jereb, M.: Aortographic Follow-up in Patients with the Bjork-Shiley Aortic Disc Valve Prosthesis, Scand. J. Thorac. Cardiovasc. Surg. 7: 1, 1973. Bonchek, L. J., and Starr, A.: Ball-Valve Prostheses: Current Appraisal of Late Results, Am. J. Cardiol. 35: 843, 1975. Brown, J. W., Myerowitz, P. D., Cann, M. S., Colvin, S. B., Mclntosh, C. L., and Morrow, A. G.: Clinical and Hemodynamic Comparisons of Kay-Shiley, StarrEdwards No. 6520, and Hancock Porcine Xenograft Mitral Valves, Surgery 76: 983, 1974. Buch, W. S., Pipkin, R. D., Hancock, W. D., and Fogarty, T. J.: Mitral Valve Replacement With the Hancock-Stabilized Glutaraldehyde Valve: Clinical and Laboratory Evaluation. Presented at the Twenty-third Scientific Meeting of the International Cardiovascular Society, Boston, Mass., June 19-20, 1975. Carpentier, A., and Dubost, C : From Xenograft to Bioprosthesis: Evolution of Concepts and Techniques of Valvular Xenografts, in lonescu, M. I., Ross, D. N., and Wooler, G. H., editors: Biological Tissue in Heart Valve Replacement, London, 1972, Butterworth & Co., Ltd., p. 515. Cohn, L. H., Lamberti, J. J., Castaneda, A. R., and Collins, J. J., Jr.: Cardiac Valve Replacement With the Stabilized Glutaraldehyde Porcine Aortic Valve: Indications, Operative Results, and Follow-up. Presented at the Fortieth American College of Chest Physicians, New Orleans, Louisians, Nov. 3-6, 1974. Davila, J. C : Experience With the Hancock Porcine Xenograft for Mitral Replacement. Presented at the Second Henry Ford Hospital International Symposium on Cardiac Surgery, Detroit, Mich., Oct. 6-9, 1975. Ellis, L. B., Singh, J. B., Morales, D. D., and Harken, D. E.: Fifteen to Twenty Years Study of One Thousand Patients Undergoing Closed Mitral Valvuloplasty, Circulation 48: 357, 1973. Fernandez, J., Morse, D., Spagna, P., Lemole, G., Gooch, A., Sang-Yang, S., and Maranhao, V.: Results of Mitral Valve Replacement With the Beall Prosthesis in 209 Patients, J. THORAC. CARDIOVASC. SURG. 71:
218,
1976. 12 Freeman, R.: Microbiological Aspects of Open Heart Surgery: Diagnosis and Management, in lonescu, M. I., and Wooler, G. H., editors: Current Techniques in Extracorporeal Circulation, London, 1976, Butterworth & Co., Ltd., p. 369. 13 Gott, V. L., Brawley, R. K., and Jones, M.: Mitral Valve Prostheses: The Problem of Thromboembolism. Presented at the Second Henry Ford Hospital Interna-
Volume 73 Number 1 January, 1977
tional Symposim on Cardiac Surgery, Detroit, Mich., Oct. 6-9, 1975. 14 Horowitz, M. S.: Discussion of Johnson et al.23 15 Horowitz, M. S., Goodman, D. J., Fogarty, T. J., and Harrison, D. C : Mitral Valve Replacement With the Glutaraldehyde-Preserved Porcine Heterograft: Clinical, Hemodynamic, and Pathological Correlations, J. THORAC. CARDIOVASC. SURG. 67: 885, 1974.
16 Hume, M., Sevitt, S., and Thomas, D. P.: Venous Thrombosis and Pulmonary Embolism, Cambridge, Mass., 1970, Harvard University Press, p. 455. 17 lonescu, M. I., and Mary, D. A. S.: Which Valve Should 1 Use? Durability of Mitral Valve Substitutes. Presented at the Second Henry Ford Hospital International Symposium on Cardiac Surgery, Detroit, Mich., Oct. 6-9, 1975. 18 lonescu, M. I., Mary, D. A. S., and Abid, A.: Tissue Heart Valves: Appraisal of Late Results, in Stalpaert, G., Suy, R., and Vermeulen, F., editors: Late Results of Valvular Replacements and Coronary Surgery, Ghent, 1976, European Press, p. 56. 19 lonescu, M. I., Pakrashi, B. C , Holden, M. P., Mary, D. A., and Wooler, G. H.: Results of Aortic Valve Replacement With Frame-Supported Fascia Lata and Pericardial Grafts, J. THORAC. CARDIOVASC. SURG. 64:
340, 1972. 20 lonescu, M. I., Pakrashi, B. C , Mary, D. A. S., Bartek, I. T., and Wooler, G. H.: Long-Term Evaluation of Tissue Valves, J. THORAC. CARDIOVASC. SURG. 68: 361,
1974. 21 Isom, O. 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.
22 Isom, O. W., Williams, C. D., Falk, E. A., Spencer, F. C , and Glassman, E.: Evaluation of Anticoagulant Therapy in Cloth-Covered Prosthetic Valves, Circulation 47: 48, 1973 (Suppl. III). 23 Johnson, A. D., Daily, P. O., Peterson, K. L., LeWinter, M., DiDonna, G. J., Blaire, G., and Niwayama, G.: Functional Evaluation of the Porcine Heterograft in the Mitral Position, Circulation 52: 40, 1975 (Suppl. I). 24 Karp, R. B., Kirkiin, J. W., Kouchoukos, N. T., and Pacifico, A. D.: Comparison of Three Devices to Replace the Aortic Valve, Circulation 50: 163, 1973 (Suppl II). 25 Kloster, F. E.: Diagnosis and Management of Complications of Prosthetic Heart Valves, Am. J. Cardiol. 35: 872, 1975. 27 Long, J. W.,Reis, R. L., Bolton, M. R., Freeman, J. A., Polunibo, R. A., Pugh, D. M., Dunn, M. I., Mclntosh, C. L., and Morrow, A. G.: Clinical and Hemodynamic Assessments of Porcine Heterograft Prostheses Mounted on Flexible Stents, Circulation 48: 75, 1973 (Suppl IV). 28 Mary, D. A. S., Pakrashi, B. C , Catchpole, R. W., and lonescu, M. I.: Tissue Valves in the Mitral Position: Five Years' Experience, Br. Heart J. 37: 1123, 1975.
Valve replacement
with pericardial xenograft
41
29 Mclntosh, C. L., Michaelis, L. L., Itscoitz, S. B., Redwood, D. R., Epstein, S. E., and Morrow, A. G.: Atrioventricular Valve Replacement With the Hancock Porcine Xenograft: A Five-Year Clinical Experience. Presented at the Twenty-ninth Annual Meeting of the Society for Vascular Surgery, Boston, Mass., June, 20-21, 1975. 30 Mullin, M. J., Engelman, R. M., Isom, O. W., Boyd, A. D., Glassman, E., and Spencer, F. C : Experience With Open Mitral Commissurotomy in 100 Consecutive Patients, Surgery 76: 974, 1974. 31 Nitter-Hauge, S., Hall, K. V., Froysaker, T., and Efskind, L.: Aortic Valve Replacement: One Year Results With Lillehei-Kaster and Bjork-Shiley Disc Prosthesis: A Comparative Clinical Study, Am. Heart J. 88: 23, 1974. 32 Pipkin, R. D., Buch, W. S., and Fogarty, T. J.: Evaluation of Aortic Valve Replacement With a Porcine Xenograft Without Long-Term Anticoagulation, J. THORAC. CARDIOVASC. SURG. 71: 179, 1976.
33 Reis, R. L., Hancock, W. D., Yarbrough, J. W., Glancy, D. L., and Morrow, A. G.: The Flexible Stent: A New Concept in the Fabrication of Tissue Heart Valve Prostheses, J. THORAC. CARDIOVASC. SURG. 62: 683, 1971.
34 Technical Information on lonescu-Shiley Pericardial Xenograft Heart Valve, Shiley Laboratories, Inc. Santa Ana, Calif., 1976. 35 Starr, A., Bonchek, L. I., Anderson, R. P., Wood, J. A., and Chapman, R. D.: Late Complications of Aortic Valve Replacement With Cloth-Covered Composite-Seat Prostheses, Ann. Thorac. Surg. 19: 289, 1975. 36 Stinson, E. B., Griepp, R. B., and Shumway, N. E.: Clinical Experience With a Porcine Aortic Valve Xenograft for Mitral Valve Replacement, Ann. Thorac. Surg. 18: 391, 1974.
Discussion DR. R E G E N T
BEAUDET
Montreal, Quebec, Canada
Dr. lonescu should be congratulated for his continued effort to find a satisfactory valve replacement and also for his excellent results. We have taken a somewhat different approach, and in July, 1973, we elected to use exclusively the Lillehei-Kaster prosthesis. We made this decision because of its dynamic characteristics—its wide opening, laminar flow, and the decreased turbulence—and because of other problems that we encounter with ball valves and others. The improvement has been confirmed by our hemodynamic studies. Over the past 30 months we have inserted 112 mitral valve prostheses with an operative mortality rate of 2 per cent, the 2 deaths being related to early emboli 24 and 36 hours postoperatively. Twenty-five patients have been subjected to hemodynamic catheterization one year after valve replacement. The pulmonary pressure has decreased significantly in every patient who was restudied. The cardiac index has also improved in all patients except in 2, to an average of 0.8 L.
42
Ionescu et al.
per square meter. The mitral gradient in all of those who had pure mitral stenosis had significantly decreased following the operation. Anticoagulants were used in all except 2 patients, in whom the family physician decided to stop the medication. Both patients had cerebral emboli at 18 and 16 months postoperatively. The hemodynamic performance of the Lillehei-Kaster valve and its low incidence of embolization have justified our continued use of this prosthesis, since it compares favorably with other means of replacement presently available. D R . I O N E S C U (Closing) I should like to mention two significant points related to the results obtained with the pericardial xenograft. During the past 5 years the pericardial xenografts were constructed in our own laboratory under conditions which were less than ideal in many respects.
The Journal of Thoracic and Cardiovascular Surgery
As the results obtained with these less than ideal valves have been very good, it seems logical to expect at least similar, if not better, results with pericardial xenografts manufactured in a specialized laboratory, by improved and standardized techniques. My second point is concerned with the better quality of life obtained by patients with tissue valves than that of patients having prosthetic devices. Long-term anticoagulant treatment is not required in the great majority of these patients, and the risk of sudden, catastrophic complications is negligible indeed with tissue valves. I should like to thank my colleage and friend Regent Beaudet for reporting his results with the Lillehei-Kaster prosthesis. Vivaldi and Gershwin and Mozart and Bach are so perfectly beautiful and yet so different.
Marian I. Ionescu, M.D. (by invitation), Anand P. Tandon, M.D. (by invitation), David A. S. Mary, M.D. (by invitation), and Abdelfettah Abid, M.D. (by invitation), Leeds, England Sponsored by Dwight C. McGoon, M.D., Rochester, Minn.
O ince the beginning of heart valve replacement there have been two periods of technical development. During the first period valve replacement became established as a safe procedure. The second period has been marked by attempts to approach perfection. The clothcovered prostheses have reduced the rate of thromboembolism but have created new mechanical and hemodynamic problems.4 Although the tilting disc valves represent a step forward in valve hydraulic function, they still require prothrombin depressants.3 In the development of tissue valves an important advance has been made by the introduction of permanent tissue tanning with glutaraldehyde.7 The use of the porcine aortic valve has proved the veracity of this concept.9' 29 From the Department of Cardiothoracic Surgery, The General Infirmary, Leeds, England. Read at the Fifty-sixth Annual Meeting of The American Association for Thoracic Surgery, Los Angeles, Calif., April 23, 24, and 25, 1976. Address for reprints: Marian I. Ionescu, M.D., Department of Cardiothoracic Surgery, The General Infirmary, Great George Street, Leeds LSI 3EX, England.
In an attempt to reach the three primary goals of an ideal valve substitute, namely, freedom from thromboembolism without anticoagulation, near-normal hydraulic performance, and maintenance of long-term structural and functional integrity,17 we18 introduced in 1971 the glutaraldehyde-stabilized pericardial xenograft heart valve. This report presents our experience with pericardial xenografts inserted in 212 patients since March, 1971. Clinical material and methods During the period from March, 1971, through September, 1975, pericardial xenografts were inserted in 212 patients as single valve replacements. There were 142 patients with aortic, 67 with mitral, and 3 with tricuspid replacement. The age and sex incidence as well as the type of valve lesions are shown in Tables I and II. The mean ages were 48.7 for the aortic and 44.7 years for the mitral valve replacement group. In the aortic group there were 28 patients with additional mitral valve lesions, in the mitral group 34 patients had aortic or tricuspid lesions or both, and one patient from 31
The Journal of Thoracic and Cardiovascular Surgery
3 2 lonescu et al.
Table I. Age and sex incidence of 212 patients
Table IV. Preoperative clinical details in 212 patients
Age (yr.) Valve
11-20 21-30
Aortic Male Female Mitral Male Female Tricuspid Male Female
31-40
41-50
51-60
61-70
7 5
18 4
24 8
36 13
19 6
106 36
_
4 13
14 17
4 10
2 1
25 42
2
-
-
-
22 19
38 25
40 23
21 7
1 1
Totals Male Female
8 6
1 2 132 80
Table II. Type of valve lesion in 212 patients Aortic Valve lesion
M
F
Stenosis 36 12 Regurgitation 3 1 1 2 Mixed disease 34 10 Malfunction of 5 2 previous valve substitute
Total
Mitral M
F
Tricuspid
Total
48(47) 6 8 14(10) 43 6 5 1 1 44 (38) 13 27 40 (22) 7 - 2 2
M
F
Total
1 1 2 1 1 - - -
Legend: M, Male. F, Female. Figures in parentheses denote number of patients with valve calcification.
Table III. Etiology of valve lesion in 212 patients Aortic Rheumatic Ruptured chordae tendineae Indeterminate Congenital Endocarditis Syphilis Rheumatoid arthritis Marfan's disease Malfunction of previous valve substitute Traumatic Totals
61
-
29 23 7 3 4 8 7
Mitral
Tricuspid
60 3
2
-
1 1
-
2
Aortic
Total
-
-
-
1
142
67
3
the tricuspid group had mitral incompetence. These additional valve lesions varied from trivial to severe. The cause of the valve lesions is shown in Table III. Patients were evaluated on the basis of the New York Heart Association (N.Y.H.A.) classification, and their condition prior to operation is outlined in Table IV.
Mitral
N.Y.H.A. Class I 11 III IV
6 72 61 3
13 42 12
Syncope Angina Myocardial infarction Systemic embolism Hypertension Chronic bronchitis Epilepsy
35 78 2 5 6 8 1
3 6 1 10 2 9 5
Sinus rhythm Atrial fibrillation Complete heart block
130 8 4
17 50
Tricuspid
-
-
Table V. Concomitant surgical procedures performed at the time of valve replacement in 212 patients Surgical procedure Aorta-coronary SVBG Removal of left atrial thrombi Closure of left-to-right shunt (PDA, ASD, VSD) Wedge resection of left ventricular outflow tract Ascending aorta replacement Mitral commissurotomy Mitral annuloplasty Decalcification of mitral valve Tricuspid annuloplasty Implantation of permanent pacemaker Totals
Aortic
Mitral
11
1 7
-
5
-
39
-
9 5 14 17
_ -
-
4 104 (74)
Tricuspid
6 2
16(15)
1 (1)
Legend: SVBG, Saphenous vein bypass graft. PDA, Patent ductus arteriosus. ASD, Atrial septat defect. VSD, Ventricular septal defect. Figures in parentheses denote number of patients with concomitant surgical procedures.
The duration of the disability ranged between 2 weeks and 8 years. In the aortic group, 2 patients had had previous open aortic valvotomy and one had had pericardiectomy. In the mitral group, 21 patients had had one or two previous closed commissurotomies and one patient had had mitral annuloplasty. At the time of valve replacement, 121 additional surgical procedures were performed in 90 patients as shown in Table V. Description of the pericardial xenograft. The pericardial xenograft used throughout this series consisted of bovine pericardium mounted as a three-cusp
Volume 73 Number 1 January, 1977
Valve replacement with pericardial xenograft
33
Table VI. Details of pericardial xenograft size, type of suturing, and perfusion duration in 212 patients Implantation diameter of xenograft (mm.) Valve
19
21
23
25
27
29
Aortic Mitral Tricuspid
1
36
57
-
36 3 -
6 52 2
12 1
-
-
Perfusion* duration (min.)
Type of sutures used
_
Interrupted
Continuous
129 5
1 46
-
Mixed
Range
12 16 3
47-300 27-186 22-65
Mean 98 56 40
♦Includes total perfusion duration required for valve replacement and concomitant surgical procedures.
valve onto a Dacron-covered titanium support frame.2 The majority of patients received valves constructed in our own laboratory. Only minor changes have been made in the configuration of the sewing rim and in the quality and concentration of the solutions used during the past 5 years. For the past few months the xenografts have been manufactured by Shiley Laboratories.* Although essentially similar to the valves initially used, the Ionescu-Shiley pericardial xenografts are now manufactured by standardized techniques, the tissue being subjected to an improved treatment of stabilization with "purified glutaraldehyde."34 The lightweight titanium frame is covered with thin Dacron velour fabric to facilitate encapsulation without increasing the bulk of the valve. The sewing rim, which contains porous Teflon fabric, has the same configuration for all valve sizes and permits insertion of the valve in both the aortic and atrioventricular positions (either sub- or supra-annular). The pericardium is obtained from calves 6 to 18 months old. From the time of collection, sterile procedures are observed during the whole process of valve manufacture. Strips of pericardium of even thickness are selected, mechanically cleaned, and washed for 3 hours in Hanks solution. The stabilization and fixation of the tissue is performed with 0.5 per cent purified glutaraldehyde buffered to pH 7.4 with 0.067M phosphate at 4° C. for 2 weeks. The native structure of the pericardial tissue is permanently stabilized by the formation of inter- and intramolecular covalent bonds between the amino groups of lysine and hydroxylysine residues (present in collagen, elastin, glycoproteins, and proteoglycans) and various forms of glutaraldehyde. The total tissue antigenicity is significantly attenuated by this chemical immobilization and stabilization process with purified glutaraldehyde. The tissue cross-link density (evaluated by temperature shrinkage techniques) is optimal when 0.5 per cent *Shiley Laboratories, Inc., Santa Ana, Calif.
purified glutaraldehyde is used as the chemical stabilizing agent. This concentration ensures complete tissue sterility. Following the stabilization with purified glutaraldehyde, the pericardium is stored in 4 per cent formaldehyde buffered to pH 5.4 with 0.2M acetate. This treatment produces optimal tissue flexibility and maintains its sterility during storage. The stabilized pericardium is mounted on the outer aspect of the frame in order to maintain intact the central opening of the valve, which is the inside diameter of the support frame. One single strip of pericardium is used for the construction of all three cusps. As a result of this technique, as well as the thinness of the tissue and the geometry of the valve and sewing rim, the orifice area-annulus diameter ratio is optimal even for the very small size aortic xenografts. Operative technique. All valve replacements were performed through a median sternotomy by use of euthermic conventional cardiopulmonary bypass. For aortic valve replacement, 122 patients had left coronary perfusion and 17 patients both left and right coronary perfusion and the heart was allowed to contract. In 3 patients hypothermic arrest was used. For mitral replacement, intermittent hypoxia with local hypothermia was the routine procedure. The size of the xenografts used, the type of suturing for implantation, and the duration of cardiopulmonary bypass are shown in Table VI. Results The definition of terms used is as reported in previous publications.19, 28 Standard statistical formulas were used for the analysis of results. Early death. Seventeen patients (8.1 per cent) died between the first and forty-fifth day following operation. There were 11 deaths (7.7 per cent) in the aortic and 6 (8.9 per cent) in the mitral valve replacement group. The causes of early deaths are shown in Table VII. Follow-up. All hospital survivors, with the exception
The Journal of Thoracic and Cardiovascular Surgery
3 4 Ionescu et al.
- l - S PERCAROAL XENOGRAFT-
-l-SPERCARCXAI. XENOGRAFT-
%
MITRAL REPLACEMENT
AORTIC REPLACEMENT
100
,^_
90
100
SURVIVAL RATE (2)
(4)
92.37.
(1)
SURVIVAL RATE
* - N ^
90
(3)
9t17.
(1)
80
80 7 late deaths (5.3%)
4 late deaths (6.55%)
2 SBE.
1 S.BE
1 heart falure
2 myocardial infarction
J*
»
1 mesenteric thrombosis
1 malgnancy 1 sudden
1 dissection descending aorta 1 cusp tear 0
64
96
130
®'
2
39
3
9
46
61
34
®C
4
YEARS FOLLOW-UP
2
»
19
4
3
2
5
YEARS FOLLOW-UP
Fig. 1. Actuarial representation of expected survival rate for patients with aortic and mitral pericardial xenograft valve replacement. The number and causes of late deaths are shown for both the aortic and mitral groups. S.B.E., Subacute bacterial endocarditis.
- l - S PERICARDIAL XENOGRAFT-
- I-S PERICARDIAL XENOGRAFT-
%
AORTIC REPLACEMENT
%
100
98.3% 962% 94.4% 92.3%
100
MITRAL REPLACEMENT
%>-.
80
—
90
—
Survival Rate
—
T. Embolism
■
SBE.
—
Re-Op
"—
D. Murmur
80
®'
1
(96)
Survival Rate
*' 2
(64)
3
(39)
4
YEARS FOLLOW-UP
SMurmur S.B.E.
0 (130)
92.2%
91.1 V. 90.1%
Free of:
Free of: —
96.27,
x ^ ^- « ^
90 852%
98.1 %
\^C
©°
■—
T. Embolism
—
Re-Op
61
46
34
2
19
3
8
4
2
5
YEARS FOLLOW-UP
Fig. 2. Actuarial analysis of results following aortic and mitral pericardial xenograft valve replacement. The data are expressed as per cent expected survival rate and individual event-free curves for complications.
of one who is living abroad, have been examined by one of the authors at 6 month intervals for the entire period of follow-up. In addition to physical examination, chest radiograms and electrocardiograms were obtained at each visit. Other laboratory investigations including hemodynamic and angiographic studies were performed in a series of patients. There were 194 patients observed over a period of 6 to 61 months for a total of 5,926 months (mean 30). In the aortic group, 130 patients were observed for 3,852 months (mean 29.4); in the mitral group, 61 patients
were followed for 1,931 months (mean 31.7); and the 3 patients with tricuspid valve replacement were followed for 143 months (mean 47.3). Late death. There were 11 late deaths (5.7 per cent), 7 (5.3 per cent) with aortic and 4 (6.5 per cent) with mitral valve replacement. The causes of death are outlined in Table VIII. In 4 patients the death was related to the valve (three aortic and one mitral) and was the consequence of infective endocarditis in 3 and of a torn valve cusp in the aortic position in one patient. The actuarial analysis for survival rate in both the
Volume 73 Number 1 January, 1977
Valve replacement with pericardial xenograft
Table VII. Causes of early death in 212 patients Cause
Aortic
Cardiac Pump failure Ventricular dysrhythmia Myocardial infarction Endocarditis Noncardiac Mediastinitis Gastrointestinal hemorrhage Cerebral infarction Totals
Mitral
1 11 (7.7%)
6 (8.9%)
Table VIII. Details of late deaths in 195 hospital survivors Age (yr.)
Sex
Aortic (7 deaths M 51 M 64 M 37 M 55
Time postop. (mo.) 6 9 9 10
58
M
17
51 38
M M
24 32
Mitral (4 deaths F 58
44 46 69
F F M
8
11 11 31
Cause of death Mesenteric vein thrombosis Myocardial infarction Endocarditis, heart failure Endocarditis, reop., triple valve replacement, heart failure Acute dissection of descending aorta Myocardial infarction Cusp tear, hemolysis (three previous valve replacements), right ventricular laceration at reop. Endocarditis, reop, valve replacement, myocardial infarction Heart failure, no autopsy Sudden death, no autopsy Malignant pleural effusion, no atuopsy
Legend: F, Female. M, Male.
aortic and mitral groups is shown in Fig. 1. The predicted survival rate for patients with aortic replacement is 95.5 per cent at one year and 92.3 per cent at 3 and 5 years. For patients with mitral replacement, the predicted figures are 94.1 per cent at one year and 91.1 per cent at 3 and 6 years. Thromboembolism. Routine anticoagulant treatment was not used in this series even during the early postoperative period. All embolic episodes occurred early postoperatively, were trivial or mild, and left no sequelae. There were six instances of emboli in the
35
Table IX. Early diastolic murmurs in patients with pericardial xenograft replacement of aortic valve Diastolic murmurs Early Late Total
13(9.1%) 2(1.4%) 15(10.5%)
Valve lesion Heavily calcified aortic valve and annulus Gross dilatation of aortic annulus Associated mitral valve lesion Complex congenital anomaly of aortic root Previous aortic valve replacement
10 2 5 2 2
Clinical course Duration of follow-up with murmurs (mo.) 6-54 (17.6) No. of patients in Class I (N.Y.H.A.) 15 No change in CTR and left ventricular voltage Treatment* None 7 Hematinic agents 2 Diuretic drugs 4 Antihypertensive drugs 2 Surgical closure of perivalvular leak 1 Legend: CTR, Cardiothoracic ratio. *Perivalvular leak seen and "repaired" at initial operation in 7 patients.
entire series (1.2 episodes per 100 patient years). Valve thrombosis has not been encountered. In the aortic replacement group, 2 patients developed transient visual field defects on the fourth and sixteenth postoperative days, immediately following successful cardioversion for atrial fibrillation. One of these patients had mitral comissurotomy at the time of valve replacement. For the aortic group, the incidence of thromboembolism was 0.62 episodes per 100 patient years. Four patients in the mitral group had mild and transient pareses 3, 17, 30, and 42 days following the operation. All 4 patients were in atrial fibrillation and had a grossly enlarged left atrium. For the mitral replacement group, the incidence of thromboembolism was 2.48 episodes per 100 patient years. Actuarial analysis predicts that 98.3 per cent of patients with aortic and 92.2 per cent of patients with mitral replacement will be free of thromboembolism after 5 and 6 years, respectively (Fig. 2). Infective endocarditis. Endocarditis developed in 5 patients (2.3 per cent) in this series. There were 3 such patients in the aortic group (2.1 per cent). In one (with additional mitral annuloplasty) the infection occurred 4 months postoperatively. Antibiotic treatment was effective but reoperation was required 6 months later for heart failure. The patient died of heart failure shortly after triple valve replacement. In the second patient
The Journal of Thoracic and Cardiovascular Surgery
3 6 Ionescu et al.
AORTIC
n123
"■EW H
i.rr]/ PRE-OP
□
POST-OP
MITRAL
n55
-B|B III
36 ' /
I 0 I
"□' B PRE-OP
POST-OP
Fig. 3. Diagrammatic presentation of the pre- and postoperative N.Y.H.A. functional classification of 123 patients with aortic and 55 patients with mitral pericardial xenograft valve replacement. (with concomitant replacement of the ascending aorta) endocarditis developed 8 months postoperatively, following repeated dental extractions without antibiotic cover. The patient died shortly after hospital admission. In the third patient, endocarditis developed 21 months after valve replacement following respiratory tract infection. The valve was successfully replaced with another pericardial xenograft 26 months after the initial operation. The patient continues to be well. Endocarditis developed in 2 patients who had mitral valve replacement (2.9 per cent). The infections occurred one and 5 months postoperatively. Both had reoperation and valve replacement, but both died, the first of heart failure one month after reoperation and the second of myocardial infarction 3 months following reoperation. Represented actuarially, 96.2 per cent of patients in both the aortic and mitral groups are predicted to be free of infection 5 and 6 years postoperatively, respectively (Fig. 2). Reoperation. Eight patients (3.7 per cent) in the entire series underwent reoperation, 4 of them because of endocarditis or its sequelae as already described. Of the 4 remaining patients, 2 had aortic and 2 mitral replacement. One patient had a perivalvular leak which was successfully obliterated 7 months following aortic valve replacement. One other patient with aortic replacement developed a diastolic murmur and hemolysis 26 months postoperatively. During reoperation (at 32 months), irreparable laceration of the heart occurred owing to adhesions from three previous valve replacements. One cusp of the xenograft was vertically torn
for 4 mm. from the free margin downward. Except for this, the valve was essentially normal. Two patients from the mitral valve replacement group underwent successful reoperation and prosthetic valve replacement 13 and 31 months following xenograft insertion. In both patients one cusp of the valve had become disinserted from the support frame. Otherwise, the cusps looked normal. Prior to planned reoperation, the 2 patients had medical treatment for their left ventricular failure for 6 and 10 weeks, respectively. Of the 4 patients reoperated upon for mechanical defects related to the valves, 3 are alive and asymptomatic. The predicted event-free curve for reoperation is shown in Fig. 2. Murmurs. Early diastolic murmurs were heard in 15 patients (10.5 per cent) in the aortic group. In 13 (9.1 per cent) they occurred in the early postoperative period, whereas in 2 (1.4 per cent) they were noted 31 and 36 months following operation. Table IX outlines clinical and operative details concerning the patients with diastolic murmurs. In 7 patients perivalvular leaks were detected at the time of initial valve replacement and attempts were made to obliterate them. One patient had the perivalvular leak successfully closed at reoperation 7 months following xenograft insertion. All 15 patients are now in Class I (N.Y.H.A.) with no clinical deterioration or statistically significant changes in cardiothoracic ratio and electrocardiogram at a follow-up of 6 to 54 months (mean 17.6). In the mitral replacement group, there were 4 patients in whom apical systolic murmurs (three midsystolic and one pansystolic) were heard from the early postoperative period. Left ventricular angiograms performed in 3 of them did not show any regurgitation. The fourth patient died of a malignant pleural effusion 31 months postoperatively, before angiography could be performed. Thus the incidence of regurgitant murmurs in the mitral group is 1.4 per cent. The predicted event-free curve for murmurs is shown in Fig. 2. Clinical condition. Pre- and late postoperative N.Y.H.A. classifications are diagrammed in Fig. 3. Preoperatively, the majority of patients were in Classes II and III. All except 6 patients are now in Class I. Of these 6 subjects, 4 have chronic bronchitis and 2 have developed ischemic heart disease since the operation. Electrocardiographic and radiologic changes. Preoperatively, 112 patients from the aortic and 16 from the mitral replacement group were in sinus rhythm, as compared with 109 and 15, respectively, at the most recent evaluation.
Volume 73 Number 1 January, 1977
37
Valve replacement with pericardial xenograft
Table X. Preoperative and latest postoperative cardiothoracic ratio and left ventricular voltage in 180 long-term survivors with pericardial xenograft replacement of aortic & mitral valves CTR (%) Valve lesion Aortic Stenosis Incompetence Mixed disease All patients Mitral Stenosis Incompetence Mixed disease All patients
LV voltage
Preop.
Postop.
Postop.
Preop.
49.8 55.4 55.1 53.3
± ± ± ±
0.7 0.7 1.3 0.6
47.6 49.4 51.0 49.2
± ± ± ±
0.7* 0.6* 1.1* 0.5*
49.4 53.7 50.7 51.2
± ± ± ±
2.2 2.1 1.9 1.2
33.1 42.7 34.3 36.4
55.3 56.6 57.7 56.8
± ± ± ±
2.9 1.8 1.3 1.0
52.4 51.0 53.7 52.9
± ± ± ±
2.6 1.7f 1.3* 1.0*
26.7 46.7 33.8 35.0
± ± ± ±
4.5 3.3 1.9 1.7
32.7 ± 4.4 36.2 ± 3.4$ 31.9 ± 1.9
± ± ± ±
1.6* 1.9* 1.8* 1.1*
32.8 ± 1.5
Legend: Results are expressed as mean : standard error of the mean. CTR, Cardiothoracic ratio. LV, Left ventricular. ♦Highly significant (p < 0.001). tSignificant (p < 0.01). JHighly significant (p < 0.005).
Table XI. Hemodynamic data from the pre- and second postoperative investigation of patients with pericardial xenograft valve replacement Mitral
Aortic Variable Mean pulmonary wedge pressure (mm. Hg) Mean pulmonary artery pressure (mm. Hg) Cardiac index (L./min./sq. M.)
Time of study Preop. Postop. Preop. Postop. Preop. Postop.
Ejection systolic gradient (mm. Hg) Mean diastolic gradient (mm. Hg) Calculated xenograft surface area (sq. cm.) No. of patients Average time of postop. investigation (mo.) Xenograft implantation diameter
Rest 18.7 8.3 35.5 15.3 2.9 3.1 8.0
± 5.7 ±0.6 ± 9.5 ± 0.8 ± 0.1 ± 0.2 ± 0.6
1.6 ± 0.1
Exercise 25.3 18.7 50.2 27.7 4.0 4.4 17.5
± ± ± ± ± ± ±
6.5 2.0 11.7 2.6 0.6 0.3 0.1
2.1 ± 0.1
6 45 4 patients, 23 mm. 2 patients, 25 mm.
Exercise
Rest 19.5 12.7 28.1 21.8 1.9 2.3
± ± ± ± ± ±
1.5 0.6 1.7 1.2 0.1 0.1
6.2 ± 0.8 2.1 ± 0.1
39.8 29.0 59.5 39.4 3.4 3.8
± ± ± ± ± ±
4.7 1.9 7.6 2.0 0.2 0.2
15.8 ± 1.6 2.4 ± 0.1
13 47 10 patients, 27 mm. 3 patients, 29 mm.
Legend: Results are expressed as mean ± standard error of the mean.
As shown in Table X, there was a statistically significant reduction in the mean left ventricular voltage in all patients following aortic valve replacement and in those patients with preoperative pure mitral regurgitation. There was also statistically significant reduction in cardiothoracic ratio in all patients following either aortic or mitral valve replacement. Radiologically, there was no evidence of pericardial xenograft calcification during the period of follow-up. Hemodynamic investigations. Hemodynamic studies at rest and during exercise were performed in 30 patients with either aortic or mitral replacement. The
data from preoperative investigations were compared with those obtained at two separate postoperative studies performed at mean intervals of 10 and 45 months for aortic valve replacement and 14 and 47 months for mitral replacement. The detailed results of this investigation are published separately. At both the first and the second postoperative studies, the majority of patients with pericardial xenografts in the aortic or mitral positions exhibited normal resting pulmonary wedge, pulmonary artery, and left ventricular end-diastolic pressures. Negligible ejection systolic gradients were recorded across the aortic xenografts (8 mm. Hg at rest and 17.5 mm. Hg during exercise) at the second
The Journal of Thoracic and Cardiovascular Surgery
3 8 lonescu et al.
Fig. 4. Comparison between a pericardial xenograft (left) and a porcine aortic valve (right) seen from their outflow aspect. Both valves are frame mounted and both have an implantation diameter of 23 mm. A, The configuration of the valves. B, The difference in effective functional opening when the valve is tested in a pulse simulator at a flow rate of 3 L. per minute and at physiological pressures. postoperative study. There was no significant change in the gradients between the two investigations. The calculated effective xenograft surface area was 1.6 and 2.1 sq. cm. for aortic and 2.1 and 2.4 sq. cm. for mitral valves at rest and during exercise, respectively. The mean diastolic gradients across the mitral xenografts were 6.2 mm. Hg at rest and 15.8 mm. Hg during exercise. There was a significant reduction in pulmonary vascular resistance in patients with mitral replacement at both postoperative studies. Data from the pre- and the second postoperative hemodynamic investigations are given in Table XI. The competence of pericardial xenografts in both the aortic and mitral positions was confirmed by angiograms performed at the second postoperative study. Hemolysis. In patients without murmurs there was no clinical or laboratory evidence of intravascular hemolysis. The results of a specific laboratory investigation are published separately. Pathology. Ten pericardial xenografts were recovered at reoperation or autopsy, 6 to 32 months following insertion. One valve removed from the aortic position 32 months postoperative had a 4 mm. vertical tear in a cusp, near the commissure. Two valves were removed from the mitral position 13 and 31 months fol-
lowing operation. Both had one cusp detached from the support frame. With the exception of the mechanical lesions, these three valves were grossly intact. Three other valves (one mitral and two aortic) were affected by endocarditis. The remaining xenografts were essentially normal. The sewing rim and exposed Dacron surfaces were covered with a thin, glistening layer of fibrous tissue in continuity with the endocardium. Microscopic examination showed that the original histologic components of the pericardium had undergone little, if any, change when compared with unimplanted specimens. There was neither evidence of immune or inflammatory reaction nor of tissue ingrowths on the surface or in the substance of the cusps. Tricuspid valve replacement. There were no early or late deaths and no complications among the 3 patients with tricuspid valve replacement. By clinical criteria, the three pericardial xenografts are competent and functioning satisfactorily. The patients are in Class I (N.Y.H.A.). Discussion The detailed analysis of results obtained over a period of 5 years with the pericardial xenograft in both aortic and mitral positions indicates that over this
Volume 73 Number 1 January, 1977
period of follow-up the three primary goals for which this valve was created have been attained and that no additional, unexpected complications have been encountered. The early mortality rate of 8.1 per cent in the present series is similar to results reported with various other types of valve substitutes.4' 24' 32 The most important single determinant of the quality of a heart valve substitute is the record of patient survival. In this series the actuarial survival rate 5 years following operation (92.3 per cent for aortic and 91.1 per cent for mitral replacement) compares very favorably with published reports concerned with the use of both prostheses4' Ilp 21 and tissue valves.1* 6> 32' 36 There were 4 valve-related deaths in the entire series, and in 3 of them infection was the primary cause. Low thrombogenicity in the absence of anticoagulant treatment is one of the advantage of tissue valves. In the present series, prothrombin depressants were not used at any time following operation. The embolic incidence of 1.2 episodes per 100 patient years for the entire series (0.62 for aortic and 2.48 for mitral replacement) compares very favorably with that encountered following the use of prosthetic valves.13, 24, 26 Furthermore, the embolic rate in the present series is similar to that reported in patients having valve replacement with porcine xenografts, whether or not associated with early postoperative anticoagulant treatment.6' 8 ' 9 ' 32 - 36 An analysis of the emboli which occurred in this series during the 5 years preceding the operation showed an incidence of 2.4 episodes per 100 patient years (1.3 for aortic and 5 for mitral valve disease). This is clearly double the postoperative incidence. The embolic rate in the present series is similar to the incidence observed after mitral valvuloplasty.10'30 Because all emboli occurred in our patients within the first 6 postoperative weeks, it is conceivable that the present rate of embolism could be further reduced by using anticoagulants during this short period of time, especially in patients with enlarged and fibrillating atria. Thrombosis of the valve, which has been described with prostheses4' u and other tissue valves, 14,23 has not been encountered in the present series. The advantage of a low embolic rate and the absence of valve thrombosis without the use of prothrombin depressants becomes even more significant when considering the hazards of long-term anticoagulant therapy.16, 22 There were five episodes of infective endocarditis in this series. The infection developed early in 3 patients (1.4 per cent) and late postoperatively in 2 (one per cent). The early occurrence is considered to be related
Valve replacement with pericardial xenograft
39
to contamination during the surgical procedure or to obvious infections in noncardiac areas during the early postoperative period. Since 1972, we have not encountered any instances of infective endocarditis early postoperatively in our entire open-heart program. This data coincides with a complete change in bacteriologic monitoring of the patients and in the prophylactic administration of antibiotics.12 Both cases of endocarditis of late occurrence were attributed to untreated infective processes (dental manipulation and respiratory infection). In general, infective endocarditis is not related to a particular type of valve substitute. Its incidence in this series is similar to that in other published reports.21' 2 5 ' 3 5 The incidence of early diastolic murmurs (10.5 per cent) in the present series of patients with aortic valve replacement is relatively high but similar to some reports concerning both prosthetic3' 24' 31 and tissue valve replacements.1' 8 ' 32 In all 15 patients with diastolic murmurs the local anatomic circumstances were conducive to the occurrence of peri valvular leaks. In 7 of these patients, perivalvular leaks were detected before the conclusion of the operation and efforts were made to obliterate them. A perivalvular leak was indeed the cause of the murmur in the only patient who required reoperation. Until the final shape and size of the pericardial xenograft sewing rim were established, changes were made; the early models of uncushioned rims might have contributed to the occurrence of leaks. All of the patients with diastolic murmurs are asymptomatic 6 to 54 months from the appearance of the murmur. The hemodynamic stress for tissue valves is greater in the mitral area,20 and in this series there was only one patient who had an indication of mitral regurgitation. The previously mentioned evidence led us to believe that the early diastolic murmurs in this series were caused by perivalvular leaks. The pericardial xenograft satisfactorily relieves the hemodynamic abnormalities of valvular heart disease. This fact has been demonstrated by the clinical results and by cardiac catheterization. There is only one published report concerning hemodynamic data in patients with porcine valves in the aortic position, and the transaortic gradients measured in 3 of those patients at rest were, 15, 15, and 35 mm. Hg.33 In the present series the aortic gradients were negligible (5.7 to 9.5 mm. Hg at rest and 17 to 17.5 mm. Hg during exercise). This is due to the very large central opening of the pericardial xenograft and to its optimal orifice area-annulus diameter ratio when compared with porcine aortic valves (Fig. 4). This
40
The Journal of Thoracic and Cardiovascular Surgery
lonescu et al.
quality of the pericardial xenograft makes it a very useful aortic valve substitute for patients with a small aortic annulus. The hemodynamic data obtained in patients with pericardial xenografts in the mitral area compare favorably with results obtained following mitral valve replacement with prostheses 5 and porcine valves. 1 5 , 23, 27, 29 Sequential hemodynamic studies have demonstrated that the circulatory improvement obtained following operation both after aortic and after mitral valve replacement was maintained for at least 47 and 45 months, respectively. The mechanical dysfunction of pericardal xenografts in this series (1.4 per cent) was due to technical faults in the construction of the valves and not to degenerative changes of the pericardial tissue. In the aortic position, only one valve (0.7 per cent) developed a cusp tear. The resulting aortic incompetence was clinically and angiographically insignificant and did not progress over a period of 6 months. Reoperation was required because of hemolysis. From the mitral replacement group, in two valves (2.9 per cent) a cusp became disinserted from the support frame. Planned reoperation was successfully performed in both cases. Such mechanical problems should be eliminated by careful, standardized manufacture of the pericardial xenograft in a specialized laboratory. Five years' experience with heart valve replacement with the pericardial xenograft has shown, in both the aortic and mitral positions, excellent long-term clinical results. The embolic rate was very low in the absence of anticoagulant treatment. The superior hydraulic performance of this valve, especially in small aortic sizes, represents an additional advantage. Very few valve-related complications developed, and the maintenace of structural and functional integrity of the valve was demonstrated by histologic and hemodynamic investigations. Available evidence indicates that the long-term integrity and durability of glutaraldehyde-stabilized tissue is satisfactory. The very encouraging results obtained with the pericardial xenograft fully justify its wider and continued clinical use and evaluation. Addendum Since this paper was submitted, 12 patients with aortic valve replacement from the group of 15 patients with early diastolic murmurs had aortic root angiography. This investigation clearly demonstrated the presence of perivalvular leak in all 12 patients, confirming the clinical impression.
1 2 3
4
5
6
7
8
9
10
11
REFERENCES Barratt-Boyes, B. G.: Discussion of Karp et al.24 Bartek, I. T., Holden, M. P., and lonescu, M. I.: Frame-Mounted Tissue Heart Valves: Technique of Construction, Thorax 29: 51, 1974. Bjork, V. O., Henze, A., and Jereb, M.: Aortographic Follow-up in Patients with the Bjork-Shiley Aortic Disc Valve Prosthesis, Scand. J. Thorac. Cardiovasc. Surg. 7: 1, 1973. Bonchek, L. J., and Starr, A.: Ball-Valve Prostheses: Current Appraisal of Late Results, Am. J. Cardiol. 35: 843, 1975. Brown, J. W., Myerowitz, P. D., Cann, M. S., Colvin, S. B., Mclntosh, C. L., and Morrow, A. G.: Clinical and Hemodynamic Comparisons of Kay-Shiley, StarrEdwards No. 6520, and Hancock Porcine Xenograft Mitral Valves, Surgery 76: 983, 1974. Buch, W. S., Pipkin, R. D., Hancock, W. D., and Fogarty, T. J.: Mitral Valve Replacement With the Hancock-Stabilized Glutaraldehyde Valve: Clinical and Laboratory Evaluation. Presented at the Twenty-third Scientific Meeting of the International Cardiovascular Society, Boston, Mass., June 19-20, 1975. Carpentier, A., and Dubost, C : From Xenograft to Bioprosthesis: Evolution of Concepts and Techniques of Valvular Xenografts, in lonescu, M. I., Ross, D. N., and Wooler, G. H., editors: Biological Tissue in Heart Valve Replacement, London, 1972, Butterworth & Co., Ltd., p. 515. Cohn, L. H., Lamberti, J. J., Castaneda, A. R., and Collins, J. J., Jr.: Cardiac Valve Replacement With the Stabilized Glutaraldehyde Porcine Aortic Valve: Indications, Operative Results, and Follow-up. Presented at the Fortieth American College of Chest Physicians, New Orleans, Louisians, Nov. 3-6, 1974. Davila, J. C : Experience With the Hancock Porcine Xenograft for Mitral Replacement. Presented at the Second Henry Ford Hospital International Symposium on Cardiac Surgery, Detroit, Mich., Oct. 6-9, 1975. Ellis, L. B., Singh, J. B., Morales, D. D., and Harken, D. E.: Fifteen to Twenty Years Study of One Thousand Patients Undergoing Closed Mitral Valvuloplasty, Circulation 48: 357, 1973. Fernandez, J., Morse, D., Spagna, P., Lemole, G., Gooch, A., Sang-Yang, S., and Maranhao, V.: Results of Mitral Valve Replacement With the Beall Prosthesis in 209 Patients, J. THORAC. CARDIOVASC. SURG. 71:
218,
1976. 12 Freeman, R.: Microbiological Aspects of Open Heart Surgery: Diagnosis and Management, in lonescu, M. I., and Wooler, G. H., editors: Current Techniques in Extracorporeal Circulation, London, 1976, Butterworth & Co., Ltd., p. 369. 13 Gott, V. L., Brawley, R. K., and Jones, M.: Mitral Valve Prostheses: The Problem of Thromboembolism. Presented at the Second Henry Ford Hospital Interna-
Volume 73 Number 1 January, 1977
tional Symposim on Cardiac Surgery, Detroit, Mich., Oct. 6-9, 1975. 14 Horowitz, M. S.: Discussion of Johnson et al.23 15 Horowitz, M. S., Goodman, D. J., Fogarty, T. J., and Harrison, D. C : Mitral Valve Replacement With the Glutaraldehyde-Preserved Porcine Heterograft: Clinical, Hemodynamic, and Pathological Correlations, J. THORAC. CARDIOVASC. SURG. 67: 885, 1974.
16 Hume, M., Sevitt, S., and Thomas, D. P.: Venous Thrombosis and Pulmonary Embolism, Cambridge, Mass., 1970, Harvard University Press, p. 455. 17 lonescu, M. I., and Mary, D. A. S.: Which Valve Should 1 Use? Durability of Mitral Valve Substitutes. Presented at the Second Henry Ford Hospital International Symposium on Cardiac Surgery, Detroit, Mich., Oct. 6-9, 1975. 18 lonescu, M. I., Mary, D. A. S., and Abid, A.: Tissue Heart Valves: Appraisal of Late Results, in Stalpaert, G., Suy, R., and Vermeulen, F., editors: Late Results of Valvular Replacements and Coronary Surgery, Ghent, 1976, European Press, p. 56. 19 lonescu, M. I., Pakrashi, B. C , Holden, M. P., Mary, D. A., and Wooler, G. H.: Results of Aortic Valve Replacement With Frame-Supported Fascia Lata and Pericardial Grafts, J. THORAC. CARDIOVASC. SURG. 64:
340, 1972. 20 lonescu, M. I., Pakrashi, B. C , Mary, D. A. S., Bartek, I. T., and Wooler, G. H.: Long-Term Evaluation of Tissue Valves, J. THORAC. CARDIOVASC. SURG. 68: 361,
1974. 21 Isom, O. 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.
22 Isom, O. W., Williams, C. D., Falk, E. A., Spencer, F. C , and Glassman, E.: Evaluation of Anticoagulant Therapy in Cloth-Covered Prosthetic Valves, Circulation 47: 48, 1973 (Suppl. III). 23 Johnson, A. D., Daily, P. O., Peterson, K. L., LeWinter, M., DiDonna, G. J., Blaire, G., and Niwayama, G.: Functional Evaluation of the Porcine Heterograft in the Mitral Position, Circulation 52: 40, 1975 (Suppl. I). 24 Karp, R. B., Kirkiin, J. W., Kouchoukos, N. T., and Pacifico, A. D.: Comparison of Three Devices to Replace the Aortic Valve, Circulation 50: 163, 1973 (Suppl II). 25 Kloster, F. E.: Diagnosis and Management of Complications of Prosthetic Heart Valves, Am. J. Cardiol. 35: 872, 1975. 27 Long, J. W.,Reis, R. L., Bolton, M. R., Freeman, J. A., Polunibo, R. A., Pugh, D. M., Dunn, M. I., Mclntosh, C. L., and Morrow, A. G.: Clinical and Hemodynamic Assessments of Porcine Heterograft Prostheses Mounted on Flexible Stents, Circulation 48: 75, 1973 (Suppl IV). 28 Mary, D. A. S., Pakrashi, B. C , Catchpole, R. W., and lonescu, M. I.: Tissue Valves in the Mitral Position: Five Years' Experience, Br. Heart J. 37: 1123, 1975.
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29 Mclntosh, C. L., Michaelis, L. L., Itscoitz, S. B., Redwood, D. R., Epstein, S. E., and Morrow, A. G.: Atrioventricular Valve Replacement With the Hancock Porcine Xenograft: A Five-Year Clinical Experience. Presented at the Twenty-ninth Annual Meeting of the Society for Vascular Surgery, Boston, Mass., June, 20-21, 1975. 30 Mullin, M. J., Engelman, R. M., Isom, O. W., Boyd, A. D., Glassman, E., and Spencer, F. C : Experience With Open Mitral Commissurotomy in 100 Consecutive Patients, Surgery 76: 974, 1974. 31 Nitter-Hauge, S., Hall, K. V., Froysaker, T., and Efskind, L.: Aortic Valve Replacement: One Year Results With Lillehei-Kaster and Bjork-Shiley Disc Prosthesis: A Comparative Clinical Study, Am. Heart J. 88: 23, 1974. 32 Pipkin, R. D., Buch, W. S., and Fogarty, T. J.: Evaluation of Aortic Valve Replacement With a Porcine Xenograft Without Long-Term Anticoagulation, J. THORAC. CARDIOVASC. SURG. 71: 179, 1976.
33 Reis, R. L., Hancock, W. D., Yarbrough, J. W., Glancy, D. L., and Morrow, A. G.: The Flexible Stent: A New Concept in the Fabrication of Tissue Heart Valve Prostheses, J. THORAC. CARDIOVASC. SURG. 62: 683, 1971.
34 Technical Information on lonescu-Shiley Pericardial Xenograft Heart Valve, Shiley Laboratories, Inc. Santa Ana, Calif., 1976. 35 Starr, A., Bonchek, L. I., Anderson, R. P., Wood, J. A., and Chapman, R. D.: Late Complications of Aortic Valve Replacement With Cloth-Covered Composite-Seat Prostheses, Ann. Thorac. Surg. 19: 289, 1975. 36 Stinson, E. B., Griepp, R. B., and Shumway, N. E.: Clinical Experience With a Porcine Aortic Valve Xenograft for Mitral Valve Replacement, Ann. Thorac. Surg. 18: 391, 1974.
Discussion DR. R E G E N T
BEAUDET
Montreal, Quebec, Canada
Dr. lonescu should be congratulated for his continued effort to find a satisfactory valve replacement and also for his excellent results. We have taken a somewhat different approach, and in July, 1973, we elected to use exclusively the Lillehei-Kaster prosthesis. We made this decision because of its dynamic characteristics—its wide opening, laminar flow, and the decreased turbulence—and because of other problems that we encounter with ball valves and others. The improvement has been confirmed by our hemodynamic studies. Over the past 30 months we have inserted 112 mitral valve prostheses with an operative mortality rate of 2 per cent, the 2 deaths being related to early emboli 24 and 36 hours postoperatively. Twenty-five patients have been subjected to hemodynamic catheterization one year after valve replacement. The pulmonary pressure has decreased significantly in every patient who was restudied. The cardiac index has also improved in all patients except in 2, to an average of 0.8 L.
42
Ionescu et al.
per square meter. The mitral gradient in all of those who had pure mitral stenosis had significantly decreased following the operation. Anticoagulants were used in all except 2 patients, in whom the family physician decided to stop the medication. Both patients had cerebral emboli at 18 and 16 months postoperatively. The hemodynamic performance of the Lillehei-Kaster valve and its low incidence of embolization have justified our continued use of this prosthesis, since it compares favorably with other means of replacement presently available. D R . I O N E S C U (Closing) I should like to mention two significant points related to the results obtained with the pericardial xenograft. During the past 5 years the pericardial xenografts were constructed in our own laboratory under conditions which were less than ideal in many respects.
The Journal of Thoracic and Cardiovascular Surgery
As the results obtained with these less than ideal valves have been very good, it seems logical to expect at least similar, if not better, results with pericardial xenografts manufactured in a specialized laboratory, by improved and standardized techniques. My second point is concerned with the better quality of life obtained by patients with tissue valves than that of patients having prosthetic devices. Long-term anticoagulant treatment is not required in the great majority of these patients, and the risk of sudden, catastrophic complications is negligible indeed with tissue valves. I should like to thank my colleage and friend Regent Beaudet for reporting his results with the Lillehei-Kaster prosthesis. Vivaldi and Gershwin and Mozart and Bach are so perfectly beautiful and yet so different.