Late spontaneous disruption of a porcine xenograft mitral valve

Late spontaneous disruption of a porcine xenograft mitral valve Clinical, hemodynamic, echocardiographic, and pathological findings A case is presented offailure of a Hancock porcine xenograft mitral prosthesis secondary to disruption of the prosthetic leaflets. Clinical, hemodynamic, and echocardiographic evidence of prosthetic dysfunction has been correlated with operative, pathological, and ultrastructural findings. Other instances of dysfunction of this prosthesis have been reviewed. Echocardiography should be routinely employed when the diagnosis of xenograft dysfunction is entertained.

John W. Brown, M.D.,* Jeffrey M. Dunn, M.D.,* Eric Spooner, M.D.,** and Marvin M. Kirsh, M.D.,* Ann Arbor, Mich.

Although porcine xenograft valvular prostheses preserved by the stabilized glutaraldehyde process have shown excellent hemodynamic performance in most patients for periods up to five years, their long-term durability remains uncertain. Several large series describing experience with these prostheses have reported occasional instances of prosthetic disruption in patients without evidence of prosthetic endocarditis. The purpose of this report is to describe the clinical, hemodynamic, echocardiographic, and pathological findings in a patient with dysfunction of a prosthetic xenograft. To the best of our knowledge this is the first reported case in which xenograft leaflet disruption and prolapse were established by noninvasive means and confirmed by operation.

Case report At the age of 5'h years Patient A. T. underwent elective repair of an incomplete atrioventricular canal defect by approximating the anterior mitral leaflet cleft and suturing the inferior rim of the atrial defect patch to the base of the mitral leaflet. Recatheterization, performed 3 months postoperReceived for publication Oct. 12, 1977. Accepted for publication Nov. 15, 1977. Addressfor reprints: Marvin M. Kirsh, M.D., Professorof Surgery, Section of Thoracic Surgery, C7079 Out-Patient Building, Ann Arbor, Mich. 48109. *Department of Surgery, Section of Thoracic Surgery. **Department of Pediatric Cardiology.

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Fig. 1. Stimultaneous left ventricular (LV) and left atrial (LA) pressures measured intraoperatively following mitral valve replacement. atively because of congestive heart failure, showed a small residual atrial patency and moderate mitral regurgitation. At the time of reoperation the inferior margin of the patch was found to have pulled out of the mitral leaflet, so that both mitral insufficiency and an atrial septal defect resulted. Mitral valvuloplasty was performed, but this did not abolish the mitral regurgitation. One year later the patient underwent mitral valve replacement with a 27 mm. Hancock porcine xenograft prosthesis. Intraoperative simultaneous measurements of left ventricular and left atrial pressure showed no significant mitral prosthetic gradient or insufficiency (Fig. 1). After the operation the patient's clinical status improved greatly and the heart size was decreased on chest x-ray film.

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Disruption of xenograft mitral valve

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" Fig. 2. Top. Phonocardiogram before initial mitral xenograft replacement showing holosystolic murmur (hsm) and diastolic murmur (dm). Bottom, Phonocardiogram following replacement of disrupted porcine prosthesis with second porcine prosthesis. No murmurs are noted. 2 rics, Second right intercostal space. 51, First heart sound. 52, Second heart sound. Digoxin and diuretics were discontinued 3 months postoperatively and the patient had no exercise limitations. Three years later, when the patient was II years old, rapidly progressive congestive heart failure developed. Chest roentgenogram showed marked enlargement of the cardiac silhouette and pulmonary vascular congestion. At this time a Grade 5/6 holosystolic murmur was audible at the apex. A phonocardiogram confirmed these findings (Fig. 2). A standard M-mode echocardiogram showed left atrial and left ventricular dilatation and prolapse of one of the prosthetic leaflets into the left atrium (Fig. 3). Recatheterization at this time demonstrated marked mitral regurgitation without evidence of an intracardiac shunt. Simultaneous measurements of left atrial and pulmonary artery wedge (PAW) pressure showed a 20 mm. end-diastolic prosthetic gradient with large PAW V waves of 60mm. Hg (Fig. 4). The patient was reoperated upon in April, 1977. Inspection

of the mitral prosthesis (Fig. 5) showed complete disruption of one of the leaflets, which was obviously flail. Heavy calcification of all three leaflets was noted (Fig. 6). A small perforation was noted at the base of a second cusp. There was no evidence of prosthetic stenosis, as had been suggested by the preoperative catheterization (Fig. 6), nor was there evidence of periprosthetic regurgitation or of prosthetic endocarditis. The prosthesis was excised and replaced with a 25 mm. Hancock porcine xenograft. The patient's postoperative course was completely uncomplicated. A postoperative phonocardiogram (Fig. 2, bottom) shown no murmurs, and a repeat echocardiogram (Fig. 3, bottom) showed no evidence of prolapse of the prosthetic valve leaflets. The removed prosthesis failed to grow organisms on culture. Light-phase microscopic examination showed no evidence of infection. The collagen framework showed focal areas of disruption. Electron microscopic evaluation confirmed degradation of the collagen matrix (Fig. 7).

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Fig. 3. Top, M-mode echocardiogram before prosthetic replacement at level of aortic valve. A linear echo appears with the onset of systole just behind the aortic wall and then rapidly disappears anteriorly into the dense echos of the prosthetic cage with the onset of diastole. Bottom, M-mode echocardiogram after prosthetic replacement shows no evidence of prosthetic leaflet prolapse. aaw, Anterior aortic wall. paw, Posterior aortic wall. av, Aortic valve. pw, Posterior atrial wall.

Fig. 4. Simultaneous left ventricular (LV) and pulmonary artery wedge (PAW) pressures showing a 20 mm. end-diastolic gradient across the mitral prosthesis and 60 mm. PAW V waves indicating marked mitral regurgitation.

Discussion The major advantage of bioprosthetic valves is a low incidence of thromboembolic complications. However, the durability of these bioprostheses remains undetermined. Durability of the bioprosthetic valve is dependent upon three factors: (l) use of a flexible stent, (2)

tissue selection and mounting, and (3) the mode of tissue fixation and preservation. Xenograft valve prostheses preserved in mercury salt solutions, irradiated or frozen homografts or xenografts, fresh homografts, and formalin-preserved xenografts all have a high rate of tissue dysfunction. Failure of these pros-

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Fig. 5. Atrial (left) and ventricular (right) views of a porcine xenograft prosthesis removed 3 years following insertion. Disruption of one leaflet and heavy calcification of all three leaflets are seen. The superior leaflet is flail.

theses was due to degradation of collagen and elastin networks and, to a lesser extent, to infiltration of the xenograft tissue by inflammatory cells . Carpentier introduced glutaraldehyde for xenograft preservation in 1968. The markedly improved durability of the glutaraldehyde-preserved xenografts has been borne out of many recent large clinical studies.":" Excellent function of this prosthesis has been reported for up to 7 years. The improved durability of the glutaraldehyde-preserved xenograft is attributed to the speed of fixation and to the increased collagen cross linking which occurs with glutaraldehyde. Increased cross linking increases long-term flexibility and decreases biodegradation of the collagen. Only rare instances of primary tissue dysfunction to date have been reported." 5 -7 Zuhdi," in a recent review of the Hancock prosthesis, reported 13 instances of tissue dysfunction in more than 20,000 valve replacements during 6 years in 257 centers. In nine of the 13 cases positive blood cultures had been obtained in the postoperative period. In three of the four remaining cases reported by Zuhdi, severe residual hemodynamic abnormalities were present which

Fig. 6. Roentgenogram of one of the leaflets of a porcine xenograft mitral prosthesis removed 3 years after insertion .

The Journal of Thoracic and Cardiovascular Surgery

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• Fig. 7. Transmission electron micrograft of porcine xenograft removed 3 years after insertion . There is disruption and degeneration of collagen fibrils (arrows) . There are substantial edematous changes in the extracellular matrix . CF, Collagen fibril. ECM, Extracellular matrix. (Original magnification x 39, OOO.)

may have caused unusual turbulent stress on the prosthesis. Pathological findings in these 13 prostheses showed cusp perforation in seven and leaflet calcifications in six." Other isolated instances of xenograft prosthetic dysfunction have been reported. Stinson" reported one case of valve dysfunction after 1 year's insertion secondary to cusp perforations near the edge of one of the leaflets. The other leaflets were reportedly intact. Levitsky? re-

ported primary tissue failure of a Hancock prosthesis 19 months after insertion in a 9-year-old patient. All three cusps were stiff and heavily calcified. Loss of collagen and elastin integrity was confirmed by electron microscopic evaluation. McIntosh and associates" have reported two cases of primary tissue dysfunction in two patients, 3 and 56 months following insertion of a Hancock porcine prosthesis. In each tears were noted at points of attachment of the commissure to the prosthet-

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ic struts and multiple areas of dense calcification were seen. Histologic evaluation showed degradation of the collagen and elastin frameworks. Roberts" reviewed the two valves of McIntosh, one reported by Levitsky, and our own, as well as nearly 50 other Hancock valves implanted for periods from 3 months to 5 years. He states that nearly all of these prostheses show definite ultrastructural degradation of the collagen matrix and of the elastin network, with focal areas of calcification, but only rare valves have undergone frank disruption. The degree of collagen breakdown and ialcification does not appear to be related to the length of implantation. Other authors': 3, 6 have reported little change in light-phase histologic appearance in the prostheses examined 6 months to 4 years after implantation. Carpentier" feels that fatigue lesions which histologically appear on areas of collagen degeneratives and elastin fiber fragments are inevitable owing to the basic nature of the bioprosthesis itself. The majority of histologic data including our own indicate that glutaraldehyde-preserved valves are not totally stable, nonviable polymers as originally hoped but undergo a degradation process similar to that seen with other heterograft and homograft preservation methods. However, degradation appears to proceed at a much slower rate in most patients than that seen with other tissue preservation methods. The relatively early disruption of the prosthesis in our case and many other cases reviewed herein may represent some host factor or as yet unidentifiable defect in the animal tissue or tissue-mounting process. It has been suggested that these problems are secondary to inadequate rinsing of the prosthesis prior to implantation and are due to residual aldehyde radicals on the tissue.!" This seems unlikely owing to the thorough bathing which occurs in vivo. One could speculate that there is an immunologic basis for these findings. An intensified immunologic aggressiveness in these patients has been proposed but none has been identified. It is apparent (l) that the glutaraldehyde-preservation method is superior to other methods currently available; (2) that degradation of the glutaraldehyde-preserved valve tissue may occur in a similar fashion as seen with other preservation techniques but at a much slower rate; and (3) that an undetermined factor in the host, perioperative handling of the prosthesis, or flaw in the initial prosthesis is responsible for early failure of some prostheses.

In the past, the diagnosis of porcine prosthetic dysfunction has been difficult to confirm by noninvasive means. Clinical auscultation and phonocardiography are of limited value in detecting prosthetic regurgitation because a systolic murmur is usually audible following implantation. The murmur is believed to be due to turbulent flow around one of the protruding struts of the prosthesis. Echocardiographic assessment of leaflet motion of the porcine xenograft, although reported, 11 is difficult because the dense echos produced by the flexible stent hide the more delicate echos of the leaflets. The flail prosthetic leaflet in our patient was convincingly demonstrated by echocardiography at the level of the aortic root, since the leaflet prolapsed out of the region of the stent and into the left atrium (Fig. 3, top). An echocardiogram at this level should be routinely used when xenograft regurgitation is suspected. REFERENCES Horowitz MS, Goodman DJ, Fogarty TJ, Harrison DC: Mitral valve replacement with the glutaraldehydepreserved porcine heterograft. J THoRAc CARDIOVASC SURG 67:885-895, 1974 2 Mcintosh CL, Michaelis LL, Morrow AG, Itscoitz SC, Redwood DR, Epstein SE: Atrioventricular valve replacement with the Hancock porcine xenograft. A fiveyear clinical experience. Surgery 78:768-775, 1975 3 Pipkin RD, Buck WS, Fogarty TJ: Evaluation of aortic valve replacement with a porcine xenograft without longterm anticoagulation. J THoRAc CARDIOVASC SURG 71:179-186, 1976

4 Stinson EB, Griepp RB, Oyer PE, Shumway NE: Longterm experience with porcine aortic valve xenografts. J THoRAc CARDIOVASC SURG 73:54-63, 1977 5 Zuhdi H: The porcine aortic valve bioprosthesis. A significant alternative. Ann Thorac Surg 21:573-575, 1976

6 Zuhdi H, Hawley W, Voehl V, Hancock W, Carey J, Greer A: Porcineaortic valves as replacements for human heart valves. Ann Thorac Surg 17:479-491, 1974 7 Levitsky S: Discussion of Stinson et al4 8 Roberts WC: Personal communication 9 Carpentier A: Discussion of Stinson et al" 10 Hancock W: Personal communication II Block WN, Feiner JM, WickliffeC, Symbas PN, Schlant RC: Echocardiogram of the porcine aortic bioprosthesis in the mitral position. Am J Cardiol 38:293-298, 1976