Subjects

For this retrospective study, we reviewed a prospective registry of patients with BD evaluated at the Asan Medical Center (Seoul, Korea) from 1995 to 2007, and we enrolled patients who underwent open heart surgery to correct severe AR due to BD. Patients were diagnosed on the basis of clinical findings, including echocardiographic and pathologic results. Patients who did not fulfill the current ISG criteria for BD were diagnosed on the basis of the consensus determinations of a cardiologist (J.-K.S.), a rheumatologist (B.Y.), and a pathologist (I.L.), and final diagnosis was principally dependent on characteristic histologic findings of the excised aortic valve and aorta. Our study cohort consisted of 22 patients with severe AR due to BD. We have published clinical data of patients admitted until 2005 elsewhere, and the number of subjects in this study is more than two times that in the last study.

Echocardiography

All patients underwent comprehensive two-dimensional and Doppler echocardiography before initial surgery. During both transthoracic and transesophageal echocardiography, special attention was paid to the detailed evaluation of individual aortic cusps, the ascending aorta, the left ventricular outflow tract, and the interventricular septum adjacent to the aortic leaflets. Using high-resolution transesophageal echocardiographic images, patients were scored semiquantitatively (0–2) on the basis of the degree of BD involvement in three different anatomic lesions (aortic cusp, aortic pseudoaneurysm, and dissection into the adjacent interventricular septum). Aortic cusp involvement included either aneurysmal changes with redundant motion of a single cusp (grade 1; Figure 1 A, Video 1 A; view video clip online) or aneurysmal changes of more than two cusps resulting in the formation of a conglomerated mass (grade 2; Figure 1 B, Video 1 B; view video clip online). The degree of aortitis involving the ascending aorta was graded on the basis of the size of the pseudoaneurysm or echo-free space; if it was confined to one aortic cusp or the sinus of Valsalva, it was graded as 1 ( Figure 1 C, Video 1 C; view video clip online), whereas if it was large enough to extend to the sinotubular junction, it was graded as 2 ( Figure 1 D, Video 1 D; view video clip online). Grading of the dissection of the adjacent interventricular septum was based on its maximal length, with dissections < 1 cm graded as 1 ( Figures 2 A and 2 B, Videos 2 A and 2 B; view video clip online), and those ≥1 cm were graded as 2 ( Figures 2 C and 2 D, Videos 2 C and 2 D; view video clip online). The sum of the scores of each of these three criteria was used to represent the degree of BD involvement in each patient, with 6 being the maximum total score allowed ( Table 1 ).

Representative transesophageal echocardiograms showing a scoring system for BD involvement of the aortic cusp (A,B) and the ascending aorta (C,D) . Aortic cusp involvement could include either aneurysmal change with redundant motion of a single cusp (A) (grade 1) or aneurysmal changes of more than two cusps resulting in the formation of a conglomerated mass (B) (grade 2). A pseudoaneurysm or echo-free space extending beyond the sinotubular junction was graded as 2 (D) , whereas a lesion confined to one aortic cusp or the sinus of Valsalva was graded as 1 (C) . Ao , Aorta; LA , left atrium; LV , left ventricle; PA , pulmonary artery. See Videos 1 A, 1 B, 1 C, and 1 D.

Representative transesophageal echocardiograms showing a scoring system for BD involvement of the adjacent interventricular septum (IVS) at systole (A,C) and diastole (B,D) . Dissection of the adjacent IVS was graded depending on the maximal length of the dissection: dissections < 1 cm were graded as 1 (A,B) , and those ≥1 cm were graded as 2 (C,D) . Ao , Aorta; LA , left atrium; LV , left ventricle. See Videos 2 A, 2 B, 2 C, and 2 D.

Follow-Up Data

All patients underwent surgical intervention to control severe AR. The timing of surgery and the perioperative administration of anti-inflammatory drugs were determined by the attending physician after consultation with cardiac surgeons and rheumatologists. Immunosuppressive drugs included oral prednisolone (1 mg/kg/day), colchicines (1.2 mg/day), azathioprine (1–2 mg/kg/day), methotrexate (15 mg/week), and cyclophosphamide (2 mg/day). Blood concentration of C-reactive protein, erythrocyte sedimentation rate, and clinical evaluation were used to titrate these drugs. The type of surgery was also determined by a cardiac surgeon. Pathologic examination of the surgical specimens showed aortic valvulitis with fibrinous deposits, microabscesses, and extensive endothelial loss, with no evidence of microorganism or infective endocarditis, characteristics compatible with the involvement of BD. During repeat cardiac surgery, every effort was made to aggressively debride the native aortic root, with wide reconstruction using a valved conduit or aortic graft. Patients underwent regular echocardiographic follow-up every 6 or 12 months, depending on each patient’s condition.

Follow-up data through September 2009 were obtained for all patients through telephone interviews and retrospective review of findings from regular outpatient visits. Adverse events included repeat surgery for recurrent AR and cardiac death.

Statistical Analysis

Numerical variables are expressed as mean ± SD. Clinical variables were compared in patients who did and those who did not develop recurrent AR after the first operation. Between-group comparisons were performed using the Mann-Whitney U test or the Kruskal-Wallis test as appropriate. Nominal variables were compared using Fisher’s exact test. Variables with P values ≤ .10 were selected for multivariate analysis. A Cox proportional-hazards model using a backward stepwise selection process was used to determine parameters associated with development of recurrent AR after the first operation. Cumulative survival rate curves were generated using the Kaplan-Meier method and compared using the log-rank test. Receiver operating characteristic curve analysis was used to assess the optimal cutoff point for total echocardiographic score for predicting AR recurrence; the optimal cutoff value was defined as the value that gave the maximal sum of sensitivity and specificity. All P values were two sided, and P values < .05 were considered significant. All statistical analyses were performed using SPSS version 12.0 (SPSS, Inc., Chicago, IL).