Fatigue-induced failure of the Ionescu-Shiley pericardial xenograft in the mitral position

J

THoRAc CARDIOVASC SURG

87:836-844, 1984

Fatigue-Induced failure of the Ionescu-Shiley pericardial xenograft in the mitral position In vivo and in vitro correlation and a proposed classification Four patients bad signs of primary bioprosthetic dysfunction within the fourth postoperative year after mitral valve replacement with an Iooescu-Shiley pericardial xenograft; they represent approximately 9 % of patients with Ionescu-Sbiley pericardial xenograft mitral valves followed up for more than 3 years at our ilL'ititution. Pathological investigation showedsevereincompetenceof all explanted valves due to cusp tears and IaceratiolL't. Histologic study of the pericardial tissue disclosed mild to moderate collagen

degeneration, without infection or calcification. Neoendothe6al formation on the Dacron cloth of the sewing ring was either absent or minimal. The high incidenceof valvular incompetenceprompted us to try to establish a correlation betweenthe in vivo and in vitro modesof failure of the Ionescu-Sbiley pericardial xenograft. For this purpose, 10 unimplanted Ionescu-Shiley pericardial xenograft valves were tested in a fatigue test system. Severe fatigue-induced lesiOlL'i occurred in this group after an average of 29.09 ± 17.26 x 1()6 cycles; initial failure could be recognized in six of them after an average of 16.94 ± 20.12 x 1()6 cycles. Valvestested in the fatigue test system showed tears and IaceratiolL't similar to those noted in the Ionescu-Shiley pericardial xenografts obtained from the four patients (which were assumed to bave functioned for more than 100 X 10' cycles in each case), Correlation betweenresults of the fatigue testing and our clinicalexperienceenabled us to recognize four types of tears which may occur in the Ionescu-Shiley pericardial xenograft The results of this investigation showed the following: (1) Primary tissue failure of the Ionescu-Shiley pericardial xenograft may occur suddenly. (2)A classification of tears occurring in Ionescu-Sbiley pericardial xenograft valves is usefulsince the clinical presentation of patients may differ according to type and location of the lesion. (3) In the manufacture of pericardial valves, particular care must be observed in selectionof the tissue and in the frame design.(4)Improvement of the quality control is one of the clues to enbance durability of the Ionescu-Sbiley pericardial xenograft

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

h e importance of accelerated fatigue testing of prosthetic heart valves (and especially of bioprostheses) is a controversial issue.I, 2 Most of the failures of porcine bioprostheses so far reported were caused by tissue degeneration, infection, or calcification.t' However, it is From the Department of Cardiovascular Surgery (Gabbay, Bortolotti, Strom, Frater, and Wasserman) and the Department of Pathology (Factor), Albert Einstein College of Medicine, Bronx, N. Y. Received for publication May 31, 1983. Accepted for publication July 28, 1983. Address for reprints: Dr. Shlomo Gabbay, Department of Cardiothoracic Surgery, Albert Einstein College of Medicine, 1825 Eastchester Rd., Bronx, N. Y. 10461.

836

becoming evident that prostheses do break in the heart of patients as a result of fatigue, and this is true not only of mechanical or porcine valves,1,2 but also of pericardial valves, as we6 reported recently. The Ionescu-Shiley (I-S) bovine pericardial xenograft has been recognized as a valuable alternative to porcine bioprostheses. Although a better hemodynamic performance seems to be the major advantage,':" there are some indications that this valve has a lower rate of thromboembolism than the porcine heterograft"; however, long-term durability of the I-S xenograft remains a matter of concern. Whereas many reports have described the structural changes of dysfunctioning porcine bioprostheses,":" information on the mode of

Volume 87 Number 6

Ionescu-Shiley pericardial xenograft

June 1984

FTS 1

837

FTS 2

Fig. 1. Shelhigh fatigue testing system (FTS) 1 and 2. On FrS 2 only three valve chambers are seen; the other three valves are on the opposite side of the machine. See text for further description. failure of the I-S pericardial xenograft is currently lacking. The following report describes in vivo and in vitro correlations of failing I-S valves, observed during a 6 year period of clinical experience with this device. The studies demonstrate that life-threatening bioprosthetic failure may occur with a relatively high frequency and that the nature of the failure may be predicted from accelerated fatigue testing of unimplanted valves. Patients and methods Signs of bioprosthetic dysfunction developed in four patients following mitral valve replacement (MVR) with an I-S pericardial xenograft. These four patients constitute approximately 9% of the patients at our institution who have had such devices in the mitral position for more than 3 years." Three of them had isolated MVR, and one had combined mitral and aortic valve replacement (A VR); a Hancock porcine bioprosthesis was used for AYR. All patients but one, who died suddenly 3 years postoperatively, underwent successful reoperation. Five bioprostheses (four I-S and one Hancock) were available for pathological investigation. In order to establish a correlation between the in vivo and in vitro modes of failure of the I-S pericardial xenograft valve, we tested 10 unimplanted I-S bioprostheses in a fatigue test system (FrS); the sizes were as follows: 31 mID (one valve), 29 rom (three valves), 27 mm (one valve), 25 mID (three valves), and 21 rom (two valves). These bioprostheses were tested at 1,800 rpm with a closing pressure between 80 and 100 mm Hg. In each of them , the number of cycles was recorded after which severe fatigue occurred. In some of these, initial wear

could be detected; these prostheses were subsequently fatigued up to "complete rupture." To define complete rupture we have tested in vitro in our pulse duplicator' 9 two torn explanted valves, in both of which the regurgitation fraction was found to be more than 50%. Thus we define complete rupture in the FrS as a regurgitation fraction of more than 50%. For each patient, we determined the number of cycles to which the corresponding bioprosthesis had been submitted until failure occurred. The approximate number of cycles to failure was assumed considering (I) the duration of implantation before the appearance of the first symptoms most likely related to prosthetic failure; (2) the interval between valve replacement and reoperation or death; and (3) the mean heart rate through the postoperative period, obtained from the clinical records before discharge, periodic follow-up visits, and recatheterization data. Method of fatigue testing. Fatigue testing was performed with the Shelhigh FrS I and 2 (Shelhigh Inc., Hartsdale, N. Y.). Details of these devices will be presented elsewhere. Briefly, the first system includes four completely separate units (Fig. 1). Each unit is formed by an upper chamber, containing one valve and its nonmoving units, and a lower chamber, which is the vibrating part of the system. The two chambers are connected by rubber tubing, which allows the lower part to vibrate while the upper part is fixed. Shelhigh FrS 2 (Fig. 1) includes three units, each of them containing two valve chambers connected by two "pump units ." The pumps create physiological flows and pressures allowing full opening ; flow may be measured easily by placing a flow probe in one or all valve chambers. Shelhigh FrS 2 has definite advantages over FrS 1. It is more powerful and is free of vibrations even

The Journal of Thoracic and Cardiovascular Surgery

8 3 8 Gabbay et al.

Table I. Summary of clinical and surgical data Reoperation Operation Patient

2 3 4

Age. sex

Date

Disease

53, M

MI·

6/18/78

47, F 57, M 67, M

MI MSI MI,AI

9/06/78 1/10/79 9/17/79

I

Interval from [ first operation

Type

Cause

Sudden death, 3 yr postop; acute prosthetic MR

MVR (Ionescu-Shiley, 27 nun) MVR (lonescu-Shiley, 29 mm) MVR (lonescu-Shiley, 29 mm) MVR (lonescu-Shiley, 25 mm); AVR (Hancock, 23 nun)

Outcome

42 mo 38 mo 38 mo

Prosthetic MR Prosthetic MR Prosthetic MR and AR

Well Well Well

Legend: MI. Mitral incompetence. MSI, Mitral stenosis and incompetence. AI, Aortic incompetence. MYR, Mitral valve replacement. AYR. Aortic valve replacement. MR, Mitral regurgitation, AR, Aortic regurgitation. "Following bacterial endocarditis.

Table II. Hemodynamic data before reoperation or death ,--------

Parameters

Right atrial pressure" Right ventricular pressure Pulmonary artery pressure Pulmonary capillary wedge Left ventricular pressure Aortic pressure Cardiac index (Lyrnin/rn") Mitral valve area (em')

Case I

5

IL

37/9 35/17/26 29 140/20 130/70/92 5.2 1.7

Case =-2

5 37/5 36/26/22 26 105/16 107/82/92 3.5

_

Case 3

Case 4

9 49/12 47/25/35 25 127/19 124/50/82 4.0 2.5

19 92/19 87/43/60 32 132/19 128/64/100 2.6

"All pressures in millimeters of mercury.

at the highest stroke volumes and revolutions per minute. Pressures and flows may be changed and adjusted in a few seconds, and it allows testing of more valves at the same time. Both systems are provided with an additional unit which permits control of speed, temperature, and elapsed time. The mode of failure of prosthetic valves is similar in the two systems.

Results Clinical data. Table I summarizes the clinical data, surgical procedures, and outcome of these patients. The cardiac catheterization findings, prior to reoperation or death, are reported in Table II. A brief case history of each patient is presented. 1.6 A 53-year-old man had undergone MVR with a 27 mm I-S bioprosthesis because of mitral regurgitation resulting from bacterial endocarditis. Almost 2 years, 9 months later he experienced chest pain and dyspnea. Physical examination and catheterization suggested mild mitral regurgitation, interpreted as being due to "paravalvular leak," and angiography showed single coronary disease. Three months later he was admitted to another hospital with acute pulmonary edema and died before reoperation could be performed. CASE 2. A 47-year-old woman had MVR with a 29 mrn I-S CASE

xenograft because of severe mitral regurgitation. Forty-two months later she had a sudden onset of shortness of breath on effort. She was admitted to another institution where cardiac catheterization demonstrated severe prosthetic mitral regurgitation. Emergency reoperation was successfully performed. 6 CASE 3. A 57-year-old man had undergone MVR with a 29 mm I-S bioprosthesis with excellent symptomatic recovery. Three years later he started to complain of shortness of breath; following an episode of pulmonary edema he was rehospitalized. Two-dimensional echocardiography showed the presence of a flail prosthetic cusp. Following adequate medical treatment his condition improved considerably, and 2 months after the episode of acute cardiac failure he underwent successful reoperation. CASE 4. A 67-year-old man had combined MVR and A VR with a 25 mrn I-S xenograft and a 23 mm Hancock bioprosthesis, respectively. Three years later he started complaining of shortness of breath and fatigue. On admission, he was anemic and had clinical signs of prosthetic dysfunction. A cardiac catheterization confirmed the presence of both aortic and mitral regurgitation. Reoperation was undertaken approximately 2 months following the onset of symptoms, and the patient made an uneventful recovery.

Pathological findings. Gross examination of the explants showed that incompetence was the mode of

Volume 87 Number 6 June 1984

Ionescu-Shiley pericardial xenograft

839

Fig. 2. A and B, Views of the lonescu-Shiley pericardial xenograft explanted from Patient 3. Partial detachment of one cusp from the tip of the prong is apparent. Note that the sewing ring is almost devoid of neoendothelial covering. C. A large tear involvingmore than 50% of the cusp attachment to the sewing ring was found at necropsy in Patient I. D, Explanted xenograft from Patient 4, showing a similar pattern as in Patient 3 (A and B). In addition, a small "jet hole lesion" is present in another cusp.

failure of all four I-S pericardial mitral xenografts (Fig. 2). In Cases 1 (Fig. 2, q and 2, one cusp was torn along more than 50% of its attachment to the sewing ring, from the base of the leaflet to the tip of the prong. All other cusps appeared normal. In Cases 3 (Fig. 2, A and B) and 4 (Fig. 2, D), there was again detachment of one cusp. The tear included the part of the leaflet at the level of one prong, but it involved less than 50% of the leaflet insertion to the sewing ring toward its base. In Case 3, there were beginning tears of other cusps at the commissural level. In Case 4, a perforation of one cusp was present; this was considered to be a jet lesion secondary to lateral regurgitation because of the torn cusp. In this patient, incompetence of the aortic Hancock bioprosthesis because of perforation of one cusp was also noted. The Dacron cloth of the sewing ring was completely devoid of neoendothelium in two xenografts, whereas only scattered areas of cell ingrowth were present in the remaining two. Histologic study showed signs of mild to moderate collagen breakdown, particularly in the pericardium at the site of tear or perforation. Occasional inflammatory cells and lipid infiltration were noted, but no evidence of

calcifIcation or infection was present in any explant (Fig. 3). The pathological fmdings are summarized in Table III. In the same table, the morphologic changes observed in the explants have been correlated with the number of cycles to which each valve was submitted before initial dysfunction, as suggested by the onset of symptoms, up to complete failure coincident with death or reoperation. Fatigue testing (Table IV). The 10 I-S pericardial xenograft valves were fatigued to complete rupture from a minimum of 7.99 X 1()6 cycles to a maximum of 66.1 X 1()6 cycles (mean 29.09 ± 17.26 X 1()6) (Fig. 4). In six of them initial failure could be observed; this occurred from 3.0 X 106 cycles to 57.2 X 106 cycles (mean 16.94 ± 20.12 X 106) . The most frequent type of lesion observed consisted of a large tear involving more than 50% of the cusp attachment to the sewing ring, from the tip of one prong to the base of the leaflet (five valves); this lesion was anticipated by a smaller tear, midway between the tip of one prong and the base of the cusp, observed as the initial lesion in four xenografts. In one valve, both types of lesions coexisted, involving two different cusps (Fig. 4,

The Journal of Thoracic and Cardiovascular Surgery

8 4 0 Gabbay et at.

Table ill. Pathological finding in relation to the assumed number of cycles to which each valve was submitted before initial or complete failure Patient

No. of cycles to initial failure*

No. of cycles to complete failuret

99.7 X 1()6

108.8 X 1()6

2

165.8 X 106

165.8 X 1()6

3

124

XI()6

131 xI()6

4:1:

140

X 1()6

147.7 X 1()6

Gross findings

Histologic findings

Detachment of one cusp for 75% of its attachment to sewing ring from tip of prong to base Torn cusp for more than 50% of its insertion, including commissure and base Detachment of one cusp from tip of prong for less than 50% of its attachment; initial tears of other cusps at same level Torn cusp from the insertion on a prong toward base (less than 50% of its attachment involved); perforation of one cusp due to regurgitant jet lesion

Mild collagen breakdown at tear level

Moderate collagen degeneration, at site of laceration; scattered inflammatory cells Mild collagen breakdown; mild lipid infiltration

Mild collagen degeneration at site of tear and perforation; mild inflammatory cell infiltration

·Onset of symptoms related to prosthetic dysfunction. tDeath or reoperation because of prosthetic dysfunction. :j:This patient had also a Hancock aortic porcine bioprosthesis not included in this table.

Table IV. Results offatigue testing of 10 unimplanted Ionescu-Shiley xenografts Prosthesis size (mm)

No. of cycles to initial failure

21

3.0 X 1()6

21

6.48 X 1()6

No. of cycles to complete rupture

Gross findings Tear in the midsection of one cusp far from the "stress line"

33.7 X I()6

Tear of one cusp between its base and insertion to the prong

7.99 X I()6

25

44.9 X 1()6

25

34.2 X I()6

25

10.3 X 1()6

27

15XI()6

Small tear midway between base of one cusp and tip of prong Tear at the attachment of one cusp on the sewing ring, between base and prong

29 29

20 X 106

16 X I()6 57.2 X 1()6

Small tear at tip of prong

29 31

33.7 X 1()6

66.1 X I()6 14 X 1()6

9.7 X 1()6

Tear of one cusp between base of insertion and tip of prong

C). In four bioprostheses, the tear started at the site of leaflet insertion to one prong, extending subsequently toward its base in one, with detachment of less than 50% of the cusp (Fig. 4, B). Finally, one xenograft had an initial tear located in the midsection of one cusp and a

. 20.4 X I()6

Gross findings Progression of tear toward one prong; tear at attachment of another cusp, midway between base and prong Progression of tear up to complete laceration with flail leaflet Detachment of one cusp from tip of prong to base of stent Detachment of one cusp from tip of prong Progression of lesion with detachment of cusp from prong Complete rupture of cusp

Tear of one cusp at the attachment to the tip of prong Complete detachment of less than . 50% of cusp toward its base Tear of one cusp at insertion to tip of prong Detachment of more than 50% of one cusp; small tear of another cusp between base and tip of prong

tear of another cusp extending from the tip of one prong toward the base of the cusp (Fig. 4, A). The similarity of the in vivo and in vitro tears is apparent. Classification of tears in 1-8 pericardial xenografts. The recognition of ruptured 1-8 pericardial

Volume 87 Number 6 June 1984

Ionescu-Shiley pericardia/ xenograft

84 1

Fig. 3. A. Histologic section of one cusp of xenograft explanted from Patient 3. The collagen bundles of the . pericardium appear preserved and compact. B, Partially distorted and degenerated pericardial collagen fibers with evidence of plasma insudation are present in another cusp of the same xenograft. (Masson's trichrome stain , original magnification X32.)

Fig. 4. Ionescu-Shiley pericardial xenografts fatigued up to severe rupture. A, Two types of rupture coexist in this xenograft. One cusp shows a tear at its base and another one a tear extending from the tip of the prong to the .nidportion of the cusp's base. B. In this valve partial detachment of one cusp is present, involvingless than 50% of the cusp's insertion to the sewing ring. C, Initial lesion of one cusp midway between the tip of one prong and the base of the cusp on the right. The same lesion progressed to a wider tear in another cusp.

xenograft valves in the mitral position is of extreme importance because of the possibly fatal outcome of the failure. Correlation between the clinical and fatigue test fmdings enabled us to recognize different types of tears which can occur in this device. A classification of such tears is therefore suggested here (Fig. 5): Type I. The tear starts at the site of attachment of the cusp to the sewing ring, midway between one prong and the base of the leaflet (Type la). It progresses subsequently in both directions, leading to more extensive rupture involving more than 50% of the cusp insertion and resulting in a flail leaflet (Type Ib). This tear is likely to have occurred in Patients 1 and 2 after more

than 100 X 1()6 cycles. This type of rupture either may create mild regurgitation (referred to as "paravalvular leak" in Patient 1), with later sudden onset of more severe incompetence, or it may present with acute regurgitation, as in Patient 2. This is the most dangerous type of rupture because of the possibly fatal outcome. Type Ib rupture was observed in vitro in five xenografts (fatigued for an average of 23.39 ± 14.10 X 1()6 cycles). Four of these valves had evidence of the initial lesion (Type Ia) after an average of 10.37 ± 3.51 X 106 cycles. Type II. The tear starts at the level of one prong (Type IIa) and evolves subsequently to Type lIb, when

The Journal of Thoracic and Cardiovascular Surgery

8 4 2 Gabbay et al.

Type

1A

2A

g' '-$". ~',\

I .... '-.

" '"f: :

.,-

.:

g" ,:'~,\

II",

"

~," "

I

;i

18

~ •

,II'

28

,'j

',.: ... ,.....

38

3A

4A

Type

g" , g" \\1''''''--, \~'~'/'

J

',j'

'/';

-

~", 1\

"

,'I j'

48

'';

Fig. 5. Schematic drawing of the four types of cusp rupture observed in patients (Types 1 and 2) and after fatigue testing (Types 1 to 4). The left panel represents the initial lesion, which eventually progresses to that shown in the right panel. See text for detailed description.

the laceration progresses toward the base of the cusp insertion to the sewing ring, less than 50% of which is usually involved. This type of rupture probably occurred in Patients 3 and 4, in whom incompetence developed more chronically and allowed elective reoperation. The presence of initial tears of the other cusps in Patient 3 and a jet lesion of one leaflet in Patient 4 support this hypothesis (these valves being assumed to have functioned for more than 130 X 106 cycles in both patients). Type IIa lesions were noted in vitro in four xenografts after an average of 30.35 ± 20.07 X 106 cycles. In one of them the tear progressed to Type lIb rupture after a total of 66.1 X 106 cycles. Type III. The tear starts at the middle of the cusp far from the strut (Type IlIa), and extends laterally toward one or both supporting struts (Type I1Ib). A Type IlIa lesion was observed in vitro in a xenograft after 3.0 X 106 cycles and evolved to Type I1Ib 30.7 X 106 cycles later. Type IV. The tear starts at the base of the cusp (Type IVa) and then extends laterally toward the struts (Type IVb). This type of rupture was not observed in our clinical series but was noted in one xenograft fatigued for 33.7 X 106 cycles.

Discussion Biological prostheses have become increasingly popular as cardiac valve substitutes. Among these, porcine and pericardial xenografts have gained the widest acceptance, mainly owing to their low thrombogenicity and satisfactory hemodynamics.7-1I.16.17 However, the longterm durability of both is still questionable. Although the causes of porcine valve dysfunction are currently well known,":" extensive reports on the structural failure of pericardial xenografts are lacking. The I-S pericardial xenograft has been used in recent years at our institution for both AVR and MVR with excellent clinical and hemodynamic performance at medium-term follow-up.":" However, although no valves have failed in the aortic position, four patients with an I-S pericardial xenograft in the mitral position showed evidence of cusp rupture and severe regurgitation within the fourth postoperative year. This incidence of primary early failure (9% of the mitral valves followed up for 3 years or more) was considered unacceptable and temporarily led us to stop using the I-S pericardial xenograft for MVR. Our disappointing clinical experience with this prosthesis prompted us to verify whether it was possible to establish a correlation between the in vivo and in vitro modes of failure of I-S pericardial xenografts. Accordingly, a series of pericardial valves have been tested in a FTS up to "complete rupture." Interestingly enough, the types of cusp rupture which occurred in vitro reproduced those observed in patients; in vitro testing, however, resulted in two varieties of cusp tears that were not observed clinically. Furthermore, in some of the xenografts submitted to fatigue testing, we were able to identify the moment of initial failure; this allowed us to follow the subsequent progression of the lesion. The evolution of the cusp tear correlated well with the clinical history of the four patients. In fact, in Patients 1 and 2 the tear started at the site of attachment of the cusp to the sewing ring, midway between one prong and the base of the leaflet (Type la); it then progressed to a more extensive laceration, resulting in a flail leaflet (Type Ib). This lesion is probably the most dangerous one, since it may be initially misdiagnosed and result in a later fatal outcome (as in Patient 1)6or it may present with sudden severe prosthetic regurgitation (as in Patient 2). In Patients 3 and 4, the tear started at the tip of one prong (Type IIa); this lesion, which eventually progressed toward the base of the cusp (Type lIb), is believed to be more benign, since it may allow precise diagnosis and timely reoperation. Correlation between the clinical and fatigue testing

Volume 87 Number 6

Ionescu-Shiley pericardial xenograft

843

June 1984

data led to the classification of tears occurring in the I-S pericardial xenograft, which we have proposed here. We believe that such a classification is of practical importance, since the clinical presentation and evolution of such patients may be different; awareness of the various patterns of failure of this device may help others to recognize and to treat successfully patients presenting with a dysfunctioning I-S pericardial xenograft. Gross examination of the bioprosthesis explanted from our patients showed varying degrees of valve incompetence. Histologic evaluation of the pericardial tissue revealed areas of mild to moderate collagen breakdown, predominantly at the site of cusp tears, but no evidence of calcific degeneration of the tissue. The early onset of prosthetic dysfunction together with the histologic fmdings support the fact that failure of the I-S pericardial xenograft in our clinical series has to be considered mainly the result of fatigue-induced lesions rather than degeneration of the pericardial tissue. Fatigue may have occurred as a result of two different mechanisms. In patients exhibiting type I and II rupture, the lesion is likely to have been caused by the continuous hitting of the leaflet against the Dacron cloth of the supporting frame, during the closing movements of the cusps. Indeed, tears always started very close to the insertion of the cusp to the sewing ring, the latter being completely devoid or only partially covered by neoendothelium in all cases. The same mechanism may be advocated to explain the type IV lesion which, however, was not observed clinically. It is possible that, with better neointimal ingrowth, abrasive wear of the xenograft tissue may have been avoided. On the contrary, type III rupture, also noted only in vitro, may be explained by the presence of weak areas of the collagen framework, since it was located far from the base of the cusp. To correlate the in vivoand in vitro fatigue failure, we have to assume that the I-S valves individually vary in their durability and that the group of valvesthat showed early rupture (less than lOX 106 cycles) in the FTS are probably those which will fail early in the patient's heart in the mitral position. Since a I year in vivo period corresponds approximately to 40 X 106 cycles, it is clear that the ratio in vivo/in vitro is not 1:1. Comparing the average number of cycles which the four valves in this series have sustained, we can conclude that this ratio is approximately 1:12 under the condition of accelerated fatigue testing of 1,800 rpm and closing pressures of 70 to 80 mm Hg. Lowering the speed of the testing can change the ratio considerably; e.g. with a speed of 1,000 beats/min, the valves may undergo as many as two or

three times more cycles before any damage occurs, the ratio being then 1:6 or 1:4. Thus we can define the Shelhigh accelerated FTS and conditions of testing at high speeds as "accelerated accelerated fatigue testing." We have recently performed two-dimensional echocardiograms on control patients who underwent MVR with the I-S pericardial xenograft at our institution up to 6 years postoperatively, and evidence of prosthetic dysfunction was obtained only in one case. Therefore, based on these results, we have good reason to believe that the valves that last 50 X 106 cycles in the FTS can function in the patient's heart for at least 15 years without wear failure (i.e. for almost 600 X 106 cycles). We conclude that the quality control of the I-S pericardial xenograft has to establish a uniform level of durability so that all valves can reach a performance of 50 X 106 cycles in the described conditions. This can be done by both an improvement of the bioprosthetic design and by better selection and control of the pericardial tissue.

Addendum Recently, we had further experience with tearing of the cusp of the I-S valve in the mitral position in two patients, one 3 years and one 5 years after MVR. The two patients became symptomatic 2 months before admission, experiencing dyspnea and fatigue. We have developed a strict protocol for studying these patients. Physical examination can give an important clue to the type of rupture. The first patient (3 years postoperatively) had the familiar blowing pansystolic murmur of mitral regurgitation heard maximally in the left axillary region. A two-dimensional echocardiogram showed normal opening of the valve (implying that the cusps remained attached at the commissures). Type la tear was diagnosed and this was proved correct at operation. The valve was replaced with a porcine valve and the patient did very well. This type of rupture is obviouslythe most dangerous (see text). The second patient had a completely different type of systolic murmur which can be described as a "seagull murmur." This murmur appears to be characteristic of type 2b and is presumably due to the movement of blood at high flow between a closed normal cusp and the fluttering part of the torn cusp. The two-dimensionalechocardiogram showed abnormal opening of one cusp beyond the strut, this indicating a tear from the commissure. The patient underwent reoperation and again the diagnosis was correct. The patient made an excellent recovery after successful valve re-replacement. On both explanted valves the Dacron fabric covering the stent was completely devoid of any fibrin, or endothelial, coverage and the tears occurred where the pericardial tissue would have rubbed against rough layers of Dacron fabric at the maximal stress points on closure. This is a confirmation of our theory about the mechanism of rupture and might give a clue to a possible future solution to the problem.

8 44 Gabbay et al.

We wish to thank Dr. L. Mickleborough, Department of Cardiovascular Surgery, Toronto General Hospital, Toronto, Canada, for providing information on Patient 2.

2

3

4

5

6

7

8

REFERENCES Clark RE, Swanson WM, Kardos JL, Hagen RW, Beauchamp RA: Durability of prosthetic heart valves. Ann Thorac Surg 26:323, 1978 Rainer WG, Christopher RA, Sadler TR, Hilgenberg AD: Dynamic behaviour of prosthetic aortic tissue valves as viewed by high-speed cinematography. Ann Thorac Surg 28:274, 1979 Ferrans VJ, Spray TL, Billingham ME, Roberts WC: Structural changes in glutaraldehyde-treated porcine heterografts used as substitute cardiac valves. Transmission and scanning electron microscopic observations in 12 patients. Am J Cardiol 41:1159, 1978 Ferrans VJ, Boyce SW, Billingham ME, Spray TL, Roberts WC: Infection of glutaraldehyde-preserved porcine valve heterografts. Am J Cardiol 43:1123, 1979 Ferrans VJ, Boyce SW, Billingham ME, Jones M, Ishihara T, Roberts WC: Calcific deposits in porcine bioprostheses. Structure and pathogenesis. Am J Cardio146:721, 1980 Gabbay S, Factor SM, Strom J, Becker R, Frater RWM: Sudden death due to cuspal dehiscence of the IonescuShiley valve in the mitral position. J THORAC CARDIOVASC SURG 84:313, 1982 Tandon AP, Smith DR, Mary DAS, Ionescu MI: Sequential hemodynamic studies in patients having aortic valve replacement with the Ionescu-Shiley pericardial xenograft. Ann Thorac Surg 26:149, 1977 Gabbay S, McQueen DM, Yellin EL, Frater RWM: In vitro hydrodynamic comparison of mitral valve prostheses at high flow rates. J THORAC CARDIOVASC SURG 76:771, 1978

The Journal of Thoracic and Cardiovascular Surgery

9 Gabbay S, McQueen DM, Yellin EL, Frater RWM: In vitro hydrodynamic comparison of mitral valve bioprostheses. Circulation 60:Suppl 1:62, 1979 10 Becker RM, Strom J, Frishman W, Oka Y, Lin YT, Yellin EL, Frater RWM: Hemodynamic performance of the Ionescu-Shiley valve prosthesis. J THORAC CARDIOVASC SURG 80:613, 1980 11 Ionescu MI, Tandon AP, Saunders NR, Chidambaram M, Smith DR: Clinical durability of the pericardial xenograft valve: 11 years' experience, Cardiac Bioprostheses, LH Cohn, V Gallucci, eds., New York, 1982, Yorke Medical Books, p 42 12 Spray TL, Roberts WC: Structural changes in porcine xenografts used as substitute cardiac valves. Gross and histologic observations in 51 glutaraldehyde-preserved Hancock valves in 41 patients. Am J Cardiol 40:319, 1977 13 Fishbein MC, Giessen SA, Collins 11 Jr, Barsamian EM, Cohn LH: Pathologic findings after cardiac valve replacement with glutaraldehyde-fixed porcine valves. Am J Cardiol 40:331,1977 14 Valente M, Bortolotti U, Arbustini E, Talenti E, Thiene G, Gallucci V: Glutaraldehyde-preserved porcine bioprosthesis. Factors affecting performance as determined by pathologic study. Chest 83:607, 1983 15 Becker RM, Sandor L, Tindel M, Frater RWM: Medium-term follow-up of the Ionescu-Shiley heterograft valve. Ann Thorac Surg 32:120, 1981 16 Oyer PE, Miller CD, Stinson EB, Reitz BA, MorenoCabral RJ, Shumway NE: Clinical durability of the Hancock porcine bioprosthesis. J THORAC CARDIOVASC SURG 80:824, 1980 17 Cohn LH, Mudge GH, Pratter F, Collins 11 Jr: Five to eight years' follow-up of patients undergoing porcine heart valve replacement. N Engl J Med 304:258, 1981