Asian Cardiovasc Thorac Ann 2006;14:177-182
© 2006 Asia Publishing EXchange Ltd
Non-Infectious Aortitis: an Important Cause of Severe Aortic Regurgitation
Elaine MC Chau, FRCP,
Elaine Wang, MBBS1,
Clement SW Chiu, FRCS2,
Wing-Hing Chow, FRCP
Department of Cardiology
1 Department of Pathology
2 Department of Surgery Grantham Hospital Hong Kong, China
For reprint information contact: Elaine MC Chau, FRCP Tel: 852 2518 2612 Fax: 852 2518 8558 Email: echau{at}hkucc.hku.hk, Department of Cardiology, Grantham Hospital, 125 Wong Chuk Hang Road, Hong Kong, China.
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ABSTRACT
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From 1995 to 2004, 13 patients with severe aortic regurgitation due to non-infectious aortitis underwent aortic valve surgery at our center. Twenty-eight operations (18 aortic valve replacements and 10 Bentall procedures including 1 aortic root replacement with a homograft) were performed due to a high incidence of prosthetic valve or valved conduit dehiscence (54%). Steroid therapy reduced the incidence of re-operation for anastomotic dehiscence within one year from 90% to 18%. Strategies to prevent dehiscence of the prosthetic aortic valve, which include institution of immunosuppression, replacement of the diseased aorta, and monitoring inflammatory indices, are discussed.
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INTRODUCTION
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Non-infectious aortitis can cause aortic regurgitation (AR), stenosis, occlusion, or dilatation of the aorta and its branches. It may be associated with a more generalized nonspecific aortoarteritis of unknown origin (Takayasu’s disease), Behçet’s disease, or other acute inflammatory conditions.1 Giant cell or granulomatous aortitis can be seen in autoimmune diseases such as giant cell arteritis (Horton disease), rheumatoid arthritis, systemic lupus erythematosus (SLE), ankylosing spondylitis, and Reiter syndrome.2,3 Other rare causes of aortitis include Cogan syndrome (interstitial keratitis with vestibuloauditory symptoms) and relapsing polychondritis.4,5 If AR is severe, aortic valve surgery may become necessary. Sometimes, the diagnosis of aortitis may not be apparent until the time of operation or after pathological examination of the aorta. Previously, we reported 3 cases of recurrent aortic valve prosthesis dehiscence secondary to aortitis.6 Since then, we have followed the cases of severe AR due to aortitis undergoing aortic valve surgery at our institution and assessed the outcome of these patients, with particular emphasis on the effect of immunosuppression.
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PATIENTS AND METHODS
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From January 1995 until December 2004, the pathological diagnoses of all patients undergoing aortic valve surgery, either aortic valve replacement (AVR) or the Bentall procedure (replacement of the ascending aorta with a valved conduit or homograft and re-implantation of the coronary arteries), for severe AR at our institution were reviewed. Patients with AR due to intrinsic valvular disease, such as chronic rheumatic heart disease or congenital AR, infective causes such as bacterial endocarditis, and syphilis, Marfan syndrome, or aortic dissection were excluded. Patients with AR due to non-infectious aortitis were diagnosed on the basis of the clinical finding of an immunological disorder known to be associated with AR, or on evidence of acute or chronic inflammatory changes on pathological examination of the aorta after the exclusion of infectious causes such as syphilis or mycotic aneurysm.
Unless the patient was already known to have an associated autoimmune disorder or connective tissue disease, further investigations regarding the extent of the disease and the cause of the aortitis were carried out, including screening for immune markers, an aortogram, referral for rheumatological assessment, and serial monitoring of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). If there was evidence of ongoing inflammation (elevated ESR and CRP) at the time of surgery, the patient was started on corticosteroid therapy after the operation. Prednisolone was started at 0.5–1 mg·kg–1 daily for 6 to 8 weeks and then reduced by 5 mg every week until a daily dose of 15 mg was reached. A dose of 15 mg per day was given for at least 6 months before further reduction to a maintenance dose of 5 to 7.5 mg daily, depending on the levels of inflammatory indices. On tapering of the prednisolone dosage, azathioprine at 1–2 mg·kg–1 daily could be added with monitoring of the white cell count to avoid leucopenia. The dosage of immunosuppressives was adjusted according to the ESR and CRP, which were targeted at < 20 mm·h–1 and < 0.4 mg·dL–1, respectively.
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RESULTS
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There were 590 aortic valve operations during the 10-year period, including 457 cases of first-time AVR, 40 cases of redo AVR, 79 cases of first-time Bentall procedure, 14 cases of redo Bentall procedure (including 1 replacement of the aorta with a homograft). The overall incidence of redo aortic valve surgery was 9.2% (54/590). Thirteen patients with severe AR secondary to aortitis were identified. The majority (9/13) were male, and their ages ranged from 19 to 49 years (mean, 34.3 ± 8.7 years) at the time of first presentation. Twenty-eight operations (18 AVR and 10 Bentall procedures including 1 aortic root replacement) were performed on these 13 patients (Table 1
). The incidence of redo aortic valve surgery in the aortitis patients was 54% (15/28) and the reason for re-operation was severe paravalvular leakage due to dehiscence of the prosthetic valve or anastomotic dehiscence of the valved conduit. Re-operation was required in 7 of the 13 patients (54%), each requiring 2 to 5 AVR or aortic root replacement operations. Dehiscence severe enough to warrant re-operation occurred at 1 to 12 months postoperatively. Recurrent dehiscence was observed in 5 patients. The mean follow-up period was 5.8 ± 3.4 years. Six patients were diagnosed to have associated connective tissue disease, including 2 with Takayasu’s arteritis, 3 with Behçet’s disease, and 1 with SLE.
Three patients (nos. 5, 7, 11) were already on immunosuppression with steroid therapy ± cyclophosphamide for SLE, Takayasu’s disease, or Behçet’s disease at the time of the first aortic valve operation. Two of these (nos. 5, 7) did not develop dehiscence of the aortic valve prosthesis. In 9 of the 10 remaining patients, there was evidence of ongoing inflammation at the time of operation, as indicated by a thickened aortic wall or inflammatory infiltration on pathological examination of an aortic biopsy or specimen. The ESR and CRP were elevated in each of these 9 patients, without any evidence of endocarditis or positive blood cultures. These patients were started on steroid therapy once the diagnosis was made, which effectively reduced the mean ESR from 69 to 11 mm·h–1 and the mean CRP from 7.21 to 1.06 mg·dL–1 within one month of immunosuppression.
All patients have been followed up for at least one year. Dehiscence of aortic valve prostheses or valved conduits in patients not yet treated with steroids occurred within the first year. In patients not receiving steroid therapy at the time of aortic valve surgery, the incidence of dehiscence requiring re-operation within 1 year was 90% (9/10). In contrast, for patients on steroid therapy at the time of aortic valve surgery, the incidence of dehiscence requiring re-operation within 1 year was 18% (3/17; Table 2). Three patients had aortic root replacement as the first operation and none of them required re-operation. However, 7 of the 10 patients having AVR as a first operation required re-operation; 5 had larger valves inserted at re-operation, corresponding to a gradual increase in the diameter of the aortic root and annulus. The re-operation rate within 1 year after AVR was 59% (10/17), whereas the re-operation rate within 1 year after aortic root replacement was 20% (2/10; Table 2).
Surgical and histological findings in the aortic valve and aorta are shown in Table 3. During surgery, the aorta was abnormally thickened (up to 10 mm in patient no. 9) in 9 patients. Three patients (nos. 3, 4, 6) had aneurysmal dilatation of the aorta and required aortic root replacement during the first operation. Histologically, no significant aortic valve abnormalities were found in 6 patients. The aortic valves from the other 7 patients showed variable degrees of inflammatory infiltration, fibrosis, granulation tissue, and neovascularization. In 7 operations, the resected aorta was available for histological examination which confirmed the findings of aortitis with thickening and fibrosis in the intima, media, and adventitia (Figure 1), and variable degrees of inflammatory infiltration, loss of elastic tissue, medial degeneration, and thickened vasa vasorum in the adventitia (Figure 2). Biopsies of the aortic wall were performed in 10 cases, but only one showed definite aortitis. The other biopsies were non-diagnostic even in patients who subsequently required a Bentall procedure and were confirmed to have aortitis in the resected aorta.
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Figure 1. Histopathological finding of thickened aortic wall in aortitis (hematoxylin and eosin stain, magnification x 10)
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Those patients with aortitis were prone to complications from associated diseases, such as ostial vein graft stenosis in patient no. 1 with Takayasu’s disease and gastrointestinal involvement in patient no. 3 with Behçet’s disease (Table 4). Complications of immunosuppression included septicemia in 2 patients and delayed wound healing after a 4th sternotomy in one. Four patients with 3 or more aortic valve operations developed complete heart block requiring implantation of a permanent pacemaker. Both patients in this series with Takayasu’s arteritis died during follow-up. Patient no. 1 died 4 years after his 4th aortic valve operation (combined supracoronary valved conduit and coronary bypass grafting after 3 previous AVR) from ostial occlusion of the grafts to both coronary arteries and intractable heart failure. Patient no. 7 died suddenly from an unknown cause 2 years after his AVR.
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DISCUSSION
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The incidence of aortitis is seen more frequently in Asia than in the West, and all reports of surgical treatment of aortitis syndrome have come from Japan.7–10 We believe our report is the largest series on the management of severe AR due to aortitis in Chinese patients. In previous reports, there was a female preponderance in AR due to Takayasu’s disease and giant cell arteritis, as in other systemic autoimmune diseases such as rheumatoid arthritis and SLE.3,7,8 However, in our group of patients with severe AR associated with aortitis, there was a male preponderance (69%). In 7 of our 13 patients, the inflammatory process appeared to be limited to the ascending aorta only, with no other features of vasculitis or arteritis to suggest systemic involvement. The cardinal sign of pulselessness or pulsus differens in the arms, which was present in 85% of patients with Takayasu’s disease in the series reported by Ishikawa and colleagues,1 was not found in these 7 patients although the histological findings in the aorta were indistinguishable from those in patients with Takayasu’s disease. Whether this isolated aortitis is specific to the Chinese ethnic group is currently unknown. The only 2 patients in our study who died during follow-up both suffered from Takayasu’s disease. This seems to suggest that AR due to Takayasu’s disease may have a worse outcome than aortitis due to other causes.
Diagnosis of isolated aortitis as a cause of AR can be difficult because the disease may be localized to the aortic root and histopathological confirmation is not always possible. Aortic regurgitation develops because the aortic valve cusps fail to coapt due to gradual dilatation of the aortic root and annulus. Inflammation of the aorta does not always extend to the aortic valve, which can appear normal histologically. An aortic biopsy may also be unhelpful due to patchy and segmental involvement of the aorta in the inflammatory process. In patient no. 9, aortic tissue from the side near the pulmonary artery showed scarring of the adventitia and media with patchy loss of elastic tissues in the media, fibrointimal thickening, and thickened vasa vasorum, consistent with chronic aortitis, but aortic tissue from the side near the superior vena cava did not show any abnormalities. Therefore, a negative aortic wall biopsy does not rule out a diagnosis of aortitis because of the possible sampling error.
However, the diagnosis of isolated aortitis as a cause of severe AR may be suspected if there is: abnormal thickening of the aortic wall or progressive dilatation of the ascending aorta on echocardiogram; persistently raised ESR and CRP in the absence of sepsis or infection; or abnormal thickening of the aorta noted during surgery. It is important to make this diagnosis because of the high incidence of dehiscence of the aortic valve or valved conduit (54%). Once the diagnosis of aortitis is made, inflammation should be controlled with immunosuppression (high-dose steroid therapy ± azathioprine) with regular monitoring of ESR and CRP (aimed at < 20 mm·h–1 and < 0.4 mg·dL–1, respectively). Our postoperative immunosuppression protocol is effective in controlling the aortitis as shown by the rapid reduction in ESR and CRP, and reduced incidence of re-operation within 1 year. Vigilance is required for potential complications of immunosuppression including sepsis and delayed wound healing, and the side effects of long-term steroid therapy.
Replacement of the aortic root may be the treatment of choice for patients with AR due to aortitis as the re-operation rate within 1 year of aortic root replacement was lower at 20%, compared with 59% after AVR. The Bentall procedure without steroid therapy may be complicated by further dehiscence of the valved conduit (as seen in patient no. 10). There are 4 other case reports describing anastomotic dehiscence after the Bentall procedure for treatment of aortitis.11–14 Unfortunately for patient no. 10, the diagnosis of aortitis was delayed because of a misdiagnosis of culture-negative endocarditis. After the second dehiscence of the valved conduit, a homograft was chosen to replace the aortic root instead of another prosthetic valved conduit because we believe that the stress of the prosthetic valve causes tension on the anastomosis, leading to detachment from the friable and inflamed tissue. On the other hand, the homograft is soft and without the prosthetic valve, it causes less tension on the anastomosis.
It was concluded from these findings that in patients undergoing aortic valve surgery for severe AR, aortitis is an important diagnosis to make because of the high incidence of anastomotic dehiscence of prosthetic aortic valve or valved conduit if inflammation of the aorta is not controlled. Postoperative measures to prevent dehiscence of the aortic valve prosthesis include the judicious use of immunosuppression and careful monitoring of inflammatory indices and potential complications. Replacement of the aortic root may be the treatment of choice if there is significant aneurysmal dilatation of the aorta or in the case of recurrent dehiscence of aortic valve prostheses.
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REFERENCES
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ABSTRACT
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