Long-term follow-up of the Ionescu-Shiley mitral pericardial xenograft

J

THoRAc CARDIOVASC SURG

88:758-763,

1984

Long-term follow-up of the Ionescu-Shiley mitral pericardial xenograft In a group of 40 patients discharged from the hospital after mitral valve replacement with an Ionescu-Sbiley pericardial xenograft from January, 1977, to December, 1980, seven imtances of valve failure occurred. This unprecedented incidence of bioprosthetic dysfunction after mitral valve replacement with the Ionescu-Sbiley pericardialxenograft led ~ to update the foUow-up of our patients receiving this valve in the mitral position. The results of our survey showed, at 6 years postoperatively, an actuarial survival rate of 72%, an actuarial probability of being free from emboH of 62 %, and an actuarial freedom from prosthetic failure of 60 %. The explanted valves showed complete absence of the neoendotbe6al 6ning of the Dacron-covered frame and lesions resembHog those observed in Ionescu-Sbiley pericardial xenografts removed from our fatigue test system after a mean of 29 ± 17 x 106 cycles. This similarity prompteda classification of tears occurringin the mitral Ionescu-Sbiley pericardialxenograft, whichis of extreme importance, since the cHnieal presentation and outcome of patients with a failing valve differs according to the type of rupture. The lesions of the c~p observed in cHnieal specimens were possibly related to the continuous trauma of the tissueagainst the bare Dacron cloth duringclosureof the valve. It is concluded that (1)actual durability and thrombogenicity of the Ionescu-Sbiley pericardialxenograft in the mitral position needs to be carefully reassessed, (2) close foUow-up of such patients by cHnieal and two-dimensional echocardiographic evaluation is advisable after the third postoperative year, and (3) failure of the mitral Ionescu-Sbiley pericardial xenograft may occur suddenly, and awareness of this compHcation is the clue to prompt recognition and treatment of such patients.

Shlomo Gabbay, M.D., Uberto Bortolotti, M.D., Fred Wasserman, M.A., Nathaniel Tindel, B.S., Stephen M. Factor, M.D. and Robert W. M. Frater, M.B., Ch.B., Bronx, N. Y.

h e first Ionescu-Shiley pericardial xenograft (ISPX) was implanted in our institution in January, 1977, and the results obtained with this device were shown to compare favorably with those of others, with no instances of valve dysfunction up to 4 years postoperatively.!? However, shortly after publication of our data.t' the first case of mechanical failure of a mitral ISPX was noted in our series." Subsequently, six other similar cases occurred, all involving mitral ISPX valves, which showed morphologic patterns strikingly similar to those noted in other ISPX valves removed from our fatigue test system after significant rupture had occurred." From the Departments of Cardiothoracic Surgery and Pathology, Albert Einstein College of Medicine, Bronx, N. Y. Received for publication July 5, 1984. Accepted for publication Aug. I, 1984. Address for reprints: Shlomo Gabbay, M.D., Department of Cardiothoracic Surgery, Albert Einstein College of Medicine, 1825 Eastchester Rd., Bronx, N. Y. 10461.

758

These fmdings prompted us to reassess and define the performance and durability of this device.

Methods Patient population. Forty patients discharged from the hospital after MVR with an ISPX performed between January, 1977, and December, 1980, and with a minimum follow-up of 3 years, are included in this review. There were 21 men and 19 women, ranging in age from 27 to 74 years (mean 52); only two of them were less than 30 years old. Twenty patients were in New York Heart Association (NYHA) Functional Class III and 20 in Class IV. In addition to MVR, a few patients underwent plastic repair of the tricuspid valve and coronary artery bypass grafting. One patient of this series also received an aortic Hancock xenograft. In all cases, an ISPX mounted on a metallic stent ("old" model) was used. Postoperative evaluation. Follow-up was carried out from July to October, 1983, and most patients were seen

Volume 88 Number ~Part 1 November, 1984

Ionescu-Shiley pericardial xenograft 759

Table I. Change offunctional class among the

operative survivors NYHA

Current class in long-term survivors

class

I II

III IV

20 20

26

22

II 1*

4

2*

Legend: NYHA, New York Heart Association. *All three patients died of congestive heart failure postoperatively.

and personally interviewed; in a few cases information was gathered by means of questionnaires, telephone calls, or contact with the referring physician. Criteria for diagnosis of valve failure were basically those used by the Stanford group. 10. II All cases of valve dysfunction, both primary or following infection, leading to reoperation or death were considered as major events; systemic thromboembolic episodes (TEs) resulting in permanent deficits and severe anticoagulant-related hemorrhages necessitating hospitalization were labeled as major events as well. Minor events were considered all TEs with no sequelae or transient hemorrhagic complications not necessitating special treatment. All patients were maintained on oral anticoagulants for the first 6 weeks after MVR. Indications for long-term oral anticoagulation were chronic atrial fibrillation associated with an enlarged left atrium and proved or suspected postoperative embolic episodes. Data concerning patient survival, incidence of embolism, and valve failure (presented as mean ± standard deviation) were analyzed according to actuarial meth-

ods." In vitro testing. Ten unimplanted ISPX valves were fatigued with the Shelhigh fatigue test system until significant rupture occurred. Five were "old" model valves and five were "new" model (low-profile Delrin flexible stent) ISPXs. Tests were performed at 1,600 to 1,800 rpm with a closing pressure ranging from 80 to 100 mm Hg. Complete rupture of the valve in the fatigue test system was defined when the regurgitant fraction was found to be more than 50%.9 Details on the techniques and fatigue test system are described else-

where." Results Late deaths and foUow-up. Twelve patients (30%) died after discharge. The cause of death was lung cancer in one, myocardial infarction in one, and it was unknown in three; furthermore, one patient died of prosthetic endocarditis, one of ISPX regurgitation, and one of

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1

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60 ± 1.5

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2

_

_'____...L.-_...J__....J I I I

3

4

5

6

YEARS POST- OP

.....

£ ~ :E

~ ::: ~

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B

100 90 80 70 60 50

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6

YEARS POST-OP

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100 90 80 70 60 50

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72 ± 1.5

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YEARS POST-OP

Fig. 1. A, Actuarial probability of being free from primary valve failure after mitral valve replacement (MVR) with the Ionescu-Shiley pericardial xenograft (ISPX). Six years after operation, 60% ± 1.5%of patients are free from bioprosthetic dysfunction. B, Actuarial freedom from thromboembolism after MVR with the ISPX. Six years postoperatively, 62% ± 1.3% of patients are free from major and minor embolic events. C, Actuarial survival after MVR with the ISPX. Survival is 72% ± 1.5% at 6 years postoperatively. Operative mortality is excluded.

cerebral hemorrhage. Three patients died of severe congestive heart failure; all of them were in either NYHA Class III or IV at the time of MVR and did not show any improvement after the operation. Finally, one patient died at reoperation, performed 48 months after initial MVR. Two patients were lost to follow-up; information available at the third postoperative year showed the development of a new murmur suggestive of

The Journal of

760

Gabbay et al.

Thoracic and Cardiovascular Surgery

Table U. Profile ofpatients with a bioprosthetic valve failure Reoperation Patient 1

2 3

Age (yr) 56 50 43

4

58

5

64

6 7

63 55

Sex

Year

M M F M M

1977 1978 1978 1979 1979

F M

1979 1980

Operation

Size 1-5 valve (mm)

69

MVR MVR MVR MVR MVR

27 27 29 29

AVR

23 (Hancock)

MVR, CABG to LAD MVR

I

Cause MR, Type IIa

I Well

Outcome

Died, 3 yr

42 38 38

25 27 27

Interval from operation (mo)

MR, Type Ib MR, Type lIb MR, Type lIb

AR 56

40

MR, Type Ia MR, Type Ia

Well

Died, 3 rno

Well

Died at reoperation

Well

Legend: MYR, Mitral valve replacement. AYR, Aortic valve replacement. MR, Mitral regurgitation. AR, Aortic regurgitation. CABG, Coronary artery bypass graft. LAD, Left anterior descending.

ISPX regurgitation in one. Twenty-six long-term survivors were followed up from 3.4 to 6.6 years (mean 4.6); currently, 22 of them have been assigned to NYHA Class I and four to Class II; the change of postoperative functional status in the operative survivors is shown in Table I. At present, 21 patients are in atrial fibrillation and five in sinus rhythm. Ten of the patients with atrial fibrillation are receiving oral anticoagulants and eight are not; the remaining three are receiving antiplatelet drugs. Only one of those in sinus rhythm is receiving anticoagulant treatment because of a postoperative embolus. Actuarial survival after MVR with the ISPX is 72% ± 1.5% at 6 years postoperatively (Fig. 1, C). TE. A total of 13 TEs were noted in 12 patients. Major TEs were diagnosed in three and minor TEs in six. One patient had two major TEs. At least half of these patients were in atrial fibrillation and receiving no anticoagulant treatment when the TE occurred. One patient was receiving anticoagulants after he had a stroke almost 2 years after MVR, while in sinus rhythm. This has been considered retrospectively as a harbinger of ISPX failure, since reoperation was undertaken 6 months later. The actuarial probability of being free from major and minor TEs at 6 years is 62% ± 1.3% (Fig. 1, B). Three patients experienced hemorrhagic complications related to the use of oral anticoagulants; two had a cerebral hemorrhage (one died and one recovered) and one had recurrent hematuria. Valve failure. Primary failure of a mitral ISPX occurred in seven patients at a mean time of 45.5 months from operation. The first patient in whom this complication was noted died 3 years postoperatively of acute prosthetic regurgitation." The other six underwent reoperation, which was successful in 5; one patient, presenting with advanced cardiac cachexia, died of low output syndrome a few hours after replacement of a

regurgitant ISPX. The clinical profile of these patients is summarized in Table II. On gross examination, in all explants, the Dacron cloth covering the inner aspect of the frame appeared completely devoid of neoendothelium (Fig. 2). Scattered islets of endothelium were noted on the sewing ring in some devices, and their presence was confirmed histologically. Tears were present in one or more leaflets, involving predominantly the tissue close to the cusp insertion to the frame. This frequently resulted in a flail leaflet with prosthetic regurgitation because of cusp and commissural detachment. Histologic examination showed complete absence of calcium deposition and well-preserved collagen framework, except in the area surrounding the tears, where mild to moderate collagen breakdown was noted. Infection of the ISPX occurred in two patients; one died 3 months after operation and one was successfully treated with antibiotics. Actuarial probability of being free from primary ISPX failure is 60% ± 1.5% at 6 years (Fig. 1, A). In vitro testing. Complete rupture of the ISPX occurred in the fatigue test system after a mean of 29 ± 17 X 106 cycles (range 8 X 106 to 66 X 106 cycles); all the valves recovered at reoperation were assumed to have functioned for more than 1()() X 1Q6 cycles. In six of 10 valves removed from the fatigue test system, an initial tear was observed and progression of the lesion was followed. Thus, tears most frequently involved the attachment of the cusp to the sewing ring extending from the tip of one strut to the base of the leaflet, similar to those observed in ISPX valves explanted from patients. (The "old" and "new" ISPX did not differ in the rate and type of failure.) Comparison between clinical and in vitro results led us to a classification of ISPX lesions that have been reported elsewhere." Briefly,the Gabbay classification of

Volume 88 Number 5. Part 1 November . 1984

Ionescu-Shiley pericardial xenograft

761

the different types of fatigue-induced lesions describe four types of ruptures. Type I showed a tear midway between the tip of one prong and the base of the cusp, near the attachment of the tissue to the sewing ring (Type la); this lesion further progressed and resulted in a flail leaflet with detachment of more than 50% of the cusp (Type Ib). In Type II lesion the tear started at the tip of one prong (Type IIa) and progressed subsequently toward the base of the cusp, which became more than 50% detached (Type lIb). Types III and W showed a tear starting at the middle of the body and at the base of one cusp (Type IlIa and IVa, respectively), extending eventually toward one or both struts (Type I1Ib and IVb). Types I and II were the only lesions observed clinically and are shown in Fig. 3. Discussion The results reported so far in patients undergoing valve replacement with the ISPX show excellent durability of this device up to 11 years postoperatively.I Dysfunction of ISPXs has been reported previously, but almost exclusively as isolated casesv"" or in larger series of young subjects'<" in whom there is notorious tendency toward early bioprosthetic calcific degeneration.17• 's Our results strikingly contrast with those of Ionescu and associates,I who report a 91% freedom from initial ISPX dysfunction at 12 years. In fact, primary failure occurred in seven of 40 patients discharged from the hospital after MVR with an ISPX and followed for at least 3 years, corresponding to a 60% actuarial probability of being free from ISPX dysfunction at 6 years. The first patient in whom failure of the ISPX occurred died almost 3 years after operation because of acute mitral regurgitation and massive pulmonary edema; 3 months previously a diagnosis of "paravalvular leak" was made and close follow-up recommended.' In retrospect, this patient is now considered to have had an initial cusp tear (Type la) which eventually progressed to sudden complete failure (Type Ib). Made alert by this experience, we were able to recognize and reoperate on six other patients with an initial failure of an ISPX. The peculiar morphologic fmding observed in the ISPXs explanted from these seven patients, coupled with the results of the fatigue testing study, showed that failure of ISPX valves was not caused by tissue degeneration, the collagen framework being fairly preserved in all specimens and there being no Ca'" present. Furthermore, we were impressed by the absence of neoendothelium on the Dacron cloth covering the inner surface of the frame; therefore, we explained the cusp tears as the consequence of the continuous hitting of the tissue

Fig. 2. Ionescu-Shiley pericardiaI xenograft explanted after 69 months from Patient I. The valve was grossly incompetent and the Dacron cloth of the frame was completely devoid of neoendothelial covering.

against the bare Dacron cloth during the closing movements of the valve," This theory is supported both by the position of the tears and by the striking similarity with the lesions observed in ISPXs removed from the fatigue test system. A better neointimal ingrowth would probably have minimized this complication. This experience therefore indicates that the ISPX when implanted in the mitral position may undergo fatigue-induced failure; interestingly enough, in a similar series of patients undergoing aortic valve replacement with the same device and followed up for the same postoperative interval, no instances of ISPX failure occurred.' This is in agreement with recent observations on the longer durability of porcine aortic versus mitral xenografts. " Probably the greater closing pressure that a three-leaflet valve bears in the mitral position results in a higher stress on the tissue and in earlier dysfunction. (Our fatigue testing experience confirms this hypothesis, since valves tested with pressures higher than 100 mm Hg rupture earlier in vitro.) Since the first cases of ISPX dysfunction were observed and since we became aware of the variety of tears occurring in these devices, we were able to diagnose correctly the type of rupture in the last three patients. We believe this to be an important issue, since the evolution of the tear and subsequent clinical presentation of these patients proved to be different. In fact, Type I lesions have a more rapid and dangerous evolution and may suddenly present as an emergency situation when complete cusp rupture occurs. On the

7 6 2 Gabbay et al.

The Journal of Thoracic and Cardiovascular Surgery

Fig. 3. A. ISPX removed from the fatigue test system. A tear is present (black arrow) midway between the tip of one' prong and the base of the cusp, close to the insertion of the tissue to the sewing ring (Type Ia). This lesion progresses and leads to detachment of more than 50% of the cusp (Type Ib), resulting in a flail leaflet (white arrow). B, ISPX explanted at reoperation after 56 months from Patient 6. An advanced Type Ia lesion is evident. C, Another pericardial xenograft removed from the fatigue test system showed a detachment of one leaflet for less than 50% of its insertion. This lesion started as a limited tear at the tip of the prong (Type IIa) and progressed to that actually shown (Type lIb) . D. Type IIa lesion was found in this xenograft explanted at reoperation after 38 months from Patient 4. The Ionescu-Shiley valves shown in A and C are the new model, low-profile pericardial xenografts. The behavior in the fatigue test system of the old and new models of ISPX valves was the same.

other hand, Type II lesions are more progressive and therefore benign, allowing enough time for recognition and reoperation. In our experience, clues to a correct differentiation of the two types of rupture were as follows: (1) the difference of murmur, which usually resembled a "regular" mitral systolic regurgitant murmur in Type Ia and appeared as a "seagull" murmur in Type IIa and (2) the valuable aid of two-dimensional echocardiography, which was negative in Type fa and diagnostic in Type IIa. When both lesions have progressed to the respective Type b pattern, two-dimensional echocardiography will show a flail leaflet, and differentiation of the two lesions will obviously become impossible on this basis. In light of our experience, we suggest a close follow-up of these patients by means of

noninvasivemethods, particularly after the third postoperative year, and recommend prompt evaluation and reoperation once a new murmur develops. Bioprosthetic valves have been associated with a low incidence of thromboembolic complications.v" Recently, the ISPX has been reported to be even less thrombogenic than the porcine heterograft.' Again, we have observed an incidence of TE after MVR with the ISPX higher than that reported by others,' who noted a 96% actuarial freedom from TEs after MVR at 12 years. In fact, in our series, the probability of being free from TEs at 6 years after MVR with the ISPX is only 62%. A possible explanation could be found in considering that the Dacron of the sewing ring, if it does not get covered by neointima, can stimulate platelet deposition and

Volume 88 Number 5, Part 1 November, 1984

thrombus formation, particularly in patients with chronic atrial fibrillation. The finding of a bare sewing ring in all explants might confirm this hypothesis. In this case, an intensive research program should be initiated to understand the mechanism of endothelialization of fabric material covering the stent, or else the Dacron should be changed altogether by a biological smooth tissue. REFERENCES

2

3

4

5

6

7

8

9

10

11

Ionescu MI, Tandon AP, Saunders NR, Chidambaram M, Smith DR: Clinical durability of the pericardial xenograft valve: II years' experience, Cardiac Bioprostheses, LH Cohn, V Gallucci, 008., New York, 1982, Yorke Medical Books, pp 42-60 Tandon AP, Smith DR, Ionescu MI: Hemodynamic evaluation of the Ionescu-Shiley pericardial xenograft in the mitral position. Am Heart J 95:595-601, 1978 Tandon AP, Smith DR, Whitaker W, Ionescu MI: Long-term hemodynamic evaluation of aortic pericardial xenograft. Br Heart J 40:602-607, 1978 Becker RM, Strom J, Frishman W, Oka Y, Lin Y, Yellin EL, Frater R WM: Hemodynamic performance of the Ionescu-Shiley valve prosthesis. J THORAC CARDIOVASC SURG 80:613-620, 1980 Tandon AP, Whitaker W, Ionescu MI: Multiple valve replacement with pericardial xenograft. Clinical and hemodynamic study. Br Heart J 44:534-540, 1980 Gonzalez-Lavin L, Chi S, Blair TC, Jung JY, Fabaz AG, McFadden PM, Lewis B, Daughters G: Five-year experience with the Ionescu-Shiley bovine pericardial valve in the aortic position. Ann Thorac Surg 36:270-280, 1983 Becker RM, Sandor L, Tindel M, Frater RWM: Medium term follow-up of the Ionescu-Shiley heterograft valve. Ann Thorac Surg 32: 120-126, 1981 Gabbay S, Factor SM, Strom J, Becker RM, Frater R WM: Sudden death due to cuspal dehiscence of the Ionescu-Shiley valve in the mitral position. J THORAC CARDIOVASC SURG 84:313-314, 1982 Gabbay S, Bortolotti D, Wasserman F, Factor S, Strom J, Frater RWM: Fatigue-induced failure of the IonescuShiley pericardial xenograft in the mitral position. In vivo and in vitro correlation and a proposed classification. J THORAC CARDIOVASC SURG 87:836-844, 1984 Oyer PE, Stinson EB, Reitz BA, Miller DC, Rossiter SJ, Shumway NE: Long-term evaluation of the porcine xenograft bioprosthesis. J THORAC CARDIOVASC SURG 78:343364, 1979 Oyer PE, Miller DC, Stinson EB, Reitz BA, Moreno-

Ionescu-Shiley pericardial xenograft 7 6 3

Cabral RJ, Shumway NE: Clinical durability of the Hancock porcine bioprosthesis. J THORAC CARDIOVASC SURG 80:824-833, 1980 12 Anderson RP, Bonchek LI, Grunkemeier GE, Lambert LE, Starr A: The analysis and presentation of surgical results by actuarial methods. J Surg Res 16:224-230, 1974 13 Ishihara T, Ferrans VJ, Jones M, Cabin HS, Roberts WC: Calcific deposits developing in a bovine pericardial bioprosthetic valve three days after implantation. Circulation 63:718-723, 1981 14 Ghosh SC, Larrieu AJ, Ablaza SG, Grana VP: Spontaneous disruption of Ionescu-Shiley bovine pericardial xenograft in the mitral position. J THORAC CARDIOVASC SURG 86:784-785, 1983 15 Galioto FM, Midgley FM, Kapur S, Perry LW, Watson DC, Shapiro SR, Ruckman RN, Scott LP III: Early failures of Ionescu-Shiley bioprosthesis after mitral valve replacement in children. J THORAC CARDIOVASC SURG 83:306-310, 1982 16 Walker WE, Duncan JM, Frazier OH, Livesay JJ, Ott DA, Reul GJ, Cooley DA: Early experience with the Ionescu-Shiley pericardial xenograft valve. Accelerated calcification in children. J THORAC CARDIOVASC SURG 86:570-575, 1983 17 Geha AS, Laks H, Stansel HC, Comhill JF, Kilman JW, Buckley MY, Roberts WC: Late failure of porcine valve heterografts in children. J THORAC CARDIOVASC SURG 78:351-364, 1979 18 Sanders SP, Levy RY, Freed MD, Norwood WI, Castaneda AR: Use of Hancock porcine xenografts in children and adolescents. Am J Cardiol 46:429-438, 1980 19 Warnes CA, Scott ML, Silver GM, Smith CW, Ferrans VJ, Roberts WC: Comparison of late degenerative changes in porcine bioprostheses in the mitral and aortic position in the same patient. Am J Cardiol 51:965-968, 1983 20 Borkon AM, McIntosh CL, Von Rueden TJ, Morrow AG: Mitral valve replacement with the Hancock bioprosthesis. Five to ten year follow-up. Ann Thorac Surg 32:128-137, 1981 21 Cohn LH, Mudge GH, Pratter F, Collins JJ Jr: Five to eight year follow-up of patients undergoing porcine heart valve replacement. N Engl J Med 304:258-262, 1981 22 Gallucci V, Valfre C, Mazzucco A, Bortolotti D, Milano A, Chioin R, Dalla Volta S, Cevese 00: Heart valve replacement with the Hancock bioprosthesis. A 5-11 year follow-up, Cardiac Bioprostheses, LH Cohn, V Gallucci, 008., New York, 1982, Yorke Medical Books, pp 9-24