Ann Thorac Surg 2005;80:1909-1911
© 2005 The Society of Thoracic Surgeons
Case report
Chronic Mitral Valve Rejection Requiring Replacement in a Nine-Year-Old Allograft
Kai Ihnken, MD
a
,
d
,
James I. Fann, MD
a
,
d
,
*
,
Thomas A. Burdon, MD
a
,
d
,
Frances L. Johnson, MD
c
,
e
,
Jon C. Kosek, MD
b
,
f
,
Norman E. Shumway, MD, PhD
a
,
d
a Department of Cardiothoracic Surgery, Stanford University, Stanford
b Department of Pathology, Stanford University, Stanford
c Division of Cardiology, Stanford University, Stanford
d Section of Cardiothoracic Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
e Section of Cardiology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
f Section of Pathology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
Accepted for publication June 4, 2004.
* Address correspondence to Dr Fann, Department of Cardiothoracic Surgery, Stanford University Medical Center, 300 Pasteur Dr, Stanford, CA94305 (Email: jfann{at}stanford.edu).
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Abstract
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A 43-year-old woman underwent mitral valve replacement for severe mitral regurgitation nine years after orthotopic heart transplant. Histopathology showed chronic rejection of the mitral valve with lymphocytic infiltrates. The patient is well at one year follow-up. This report describes an identified case of chronic mitral valve rejection requiring valve replacement.
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Introduction
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Conventional cardiac surgical procedures after orthotopic heart transplantation are generally uncommon [1–8]. Graft arteriosclerosis due to rejection and other causes comprise the majority of the posttransplant interventions. Surgery for tricuspid valve insufficiency is occasionally necessary [7, 8]. Posttransplant surgical interventions for left sided heart valves are rare, with six reported cases of mitral valve procedures for mitral insufficiency as a result of myxomatous degeneration, dilated annulus, possible endocarditis, and iatrogenic cause [1–6]. We report an identified case of chronic rejection of the mitral valve requiring valve replacement.
A 43-year-old woman who underwent orthotopic heart transplantation nine years ago for ischemic cardiomyopathy at another institution was evaluated by our cardiology service for worsening dyspnea. The cardiac valves were unremarkable at time of transplant. Two years after transplant, she was found to have a systolic murmur, and transthoracic echocardiography demonstrated mild mitral regurgitation. Routine endomyocardial biopsies in the interim showed no evidence of rejection. She had not had any previous symptoms or findings consistent with endocarditis. On evaluation, she was in New York Heart Association functional class III. Examination revealed a 3/6 holosystolic murmur. Transthoracic echocardiography indicated moderate to severe mitral regurgitation. Her immunosupression regimen included azathioprine (150 mg orally/d) and cyclosporine (150 mg orally in am and 125 mg orally in pm). She underwent endomyocardial biopsy, which showed no evidence of rejection; hemodynamic evaluation revealed a right atrial pressure of 6 mm Hg, right ventricular pressure of 29/0 mm Hg, pulmonary artery pressure of 33/16 mm Hg, pulmonary capillary wedge pressure of 14 mm Hg, and cardiac index of 2.9 L · min · m2. Coronary angiography demonstrated nonfocal coronary artery disease. Transesophageal echocardiography showed normal biventricular function and severe mitral regurgitation. Because of progressive symptoms, she underwent mitral valve operation. Intraoperatively, the valve leaflets were thickened and restricted, with commissural fusion and chordal foreshortening (Figure 1). Because valve repair was not possible, mitral valve replacement was performed using a 31 mm St Jude Medical mechanical prosthesis (St Jude Medical, Inc, St Paul, MN). Cardiopulmonary bypass time was 122 minutes and aortic cross-clamp time was 63 minutes. Postoperative course was complicated by pulmonary edema, delirium, and renal insufficiency, all of which resolved. At one year, the patient continues to be well with improved functional status.
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Fig 1. Atrial view of the mitral valve immediately after excision demonstrating thickened anterior and posterior leaflets with fused commissures.
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The mitral valve leaflets and attached chordae tendinae were fixed in 10% buffered formalin. The tissue was paraffin embedded, and sections were stained with hematoxylin and eosin, elastic van Gieson, and alcian blue. Immunohistochemical stains for CD20, CD3, and CD34 antigen expression (indicating B cell, T cell, and endothelial marker expression, respectively) were performed with a Ventana Nexes immunostainer (Ventana Medical Systems, Inc, Tucson, AZ) and monoclonal reagents (Dako Company, Carpinteria, CA). Histologic examination revealed extensive fibrosis of chordae tendinae with increased deposition of elastin, collagen, and acidic mucopolysaccharides. Vascularity was minimal. Evaluation of the mitral leaflets showed evidence of diffuse fibrosis with focal infiltrates of lymphocytes, which were almost exclusively CD3 (T cell) in type (Figure 2). There was extensive damage and focal discontinuity of endothelial cells, dystrophic fibrocytes, and extracytoplastic lysosomal fragments, all of which is consistent with chronic injury and strongly suggest chronic rejection, which on a gross level would resemble the appearance of healed rheumatic injury.
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Fig 2. High power light micrograph of the mitral valve leaflet demonstrating lymphocytic infiltrates (hematoxylin and eosin stain, x100). Immunohistochemical staining demonstrating that the lymphocytes are almost exclusively CD3+, or T cell, in type.
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Comment
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Echocardiographic evidence of tricuspid and/or mitral valve regurgitation is a common finding after cardiac transplantation [1, 7, 8]. Mitral valve dysfunction requiring surgery is rare, however. Previously, only six cases of mitral valve surgery post heart transplant were reported; three were iatrogenic injury from left ventricular endomyocardial biopsy, one from myxomatous degeneration, one case of endocarditis, and one due to dilated mitral annulus [1–6].
This report describes an identified clinical case of chronic rejection of the mitral valve. Also, there was no biopsy evidence of graft rejection, raising the possibility of valve rejection without myocyte rejection. Although the gross morphologic appearance resembles that of rheumatic valve disease, the finding of lymphocytic infiltrates staining positive for CD3 is consistent with chronic rejection of valve tissue. Hurley and Kosek [9] described chronic rejection of the atrioventricular valves in a canine model of orthotopic cardiac transplantation at 5 months without immunosupression regimen. They found no evidence of myocardial rejection, and the valves were thickened and composed of fibrous tissue with haemosiderin deposits and areas of loss of myxoid tissue. Valente and colleagues [10] evaluated the aortic root and aortic valve leaflets in 37 patients who died 2 to 4,380 days after heart and heart-lung transplantation. There were no cases of valve dysfunction; however, concomitant acute rejection of the valve leaflets and myocardium was seen in 7 cases, where T-type lymphocytic infiltrates were present. Similarly, Rajani and colleagues [11] found that homograft cardiac valves obtained from infants had an early failure rate, with histologic findings of multiple foci of inflammation consisting of T lymphocytes and B lymphocytes. They concluded that the failure of these homograft valves was consistent with rejection.
In summary, we report a patient who developed severe mitral regurgitation due to mitral valve rejection after orthotopic heart transplantation and required mitral valve replacement. The case presented further supports the clinical experience that conventional valvular procedures after orthotopic heart transplantation can be safely performed and thus avoid or delay retransplantation.
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References
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Abstract
Introduction
