Among the cardiovascular manifestations in the Marfan syndrome (MFS), aortic dissection stands out as a major cause of early mortality. The aim of this study was to test the hypothesis that patients with the MFS who experience aortic dissection differ in clinical features and outcomes from those with aortic dissection not related to the MFS. Data from patients diagnosed with aortic dissection from December 1994 to March 2009 at 1 of the major medical centers in Korea were reviewed. The clinical presentations, dissection characteristics, and outcomes of patients with and those without the MFS in a Korean population were compared. Of 445 patients with aortic dissection, 46 (10%) had the MFS. Compared to non-MFS patients, those with the MFS developed aortic dissection at younger ages (33 ± 10 vs 57 ± 13 years, p <0.001) and were less frequently hypertensive (11% vs 73%, p <0.001). During the follow-up period, patients with the MFS more often developed aortic dilatation and expansion of the dissection (39% vs 18%, p = 0.003) and showed a higher rate of reoperation (30% vs 9%, p <0.001). In conclusion, in Korean patients, aortic dissection with the MFS had different characteristics and poorer outcomes than aortic dissection without the MFS. These findings underscore the importance of accurate diagnosis and surveillance of this condition in the MFS.
The molecular defect of fibrillin-1 in the Marfan syndrome (MFS) generates a structural and functional propensity for aortic dissection. The frequency of aortic dissection in the MFS varies with age. According to a review of the International Registry of Aortic Dissection, 50% of patients with aortic dissection aged <40 years have the MFS, compared to only 2% of those aged >40 years. Aortic dissection may present significantly different features in patients with and those without the MFS. In patients with the MFS, aneurysm surveillance is essential to determine the need for surgical intervention. To our knowledge, no study has compared the clinical characteristics of aortic dissection in Asian patients with and without the MFS. The importance to improved survival of early and accurate diagnosis led us to compare the clinical profiles, anatomic characteristics, and outcomes of aortic dissection in Korean patients with and without the MFS.
Methods
We reviewed patients diagnosed with classic aortic dissection from December 1994 to March 2009 at our institute, which is 1 of the largest medical centers in Korea. Patients were followed clinically for 34 ± 35 months. Acute aortic dissection was defined as presentation of any dissection within 14 days of symptoms. Presentation of any dissection after 14 days of symptoms was classified as chronic aortic dissection. According to the Stanford classification, type A aortic dissection is defined as any dissection that involves the ascending aorta and type B as any that does not. Subjects who underwent previous cardiac surgery were not included. We excluded patients who had aortic dissection due to other causes, such as Loeys-Dietz syndrome, Ehlers-Danlos syndrome, familial thoracic aortic aneurysm and dissection, and trauma. Diagnosis of the MFS was based strictly on the presence of manifestations defined in the Ghent nosology. For accurate analysis, we did not include patients who had Marfanoid features on the basis of a physician’s judgment.
Variables of interest included demographics, medical histories, imaging results, management strategies, and clinical outcomes. Hypertension was defined as systolic blood pressure >140 mm Hg or self-reported history of hypertension with or without ongoing pharmacologic treatment. Diabetes mellitus was defined as a history of type 1 or type 2 diabetes mellitus, treated pharmacologically or controlled by diet. History of chronic renal failure was documented by chronic elevation of serum creatinine or ongoing dialysis. Previous stroke or cerebrovascular accident was defined as a history of stroke or loss of neurologic function caused by any ischemic events. According to the regurgitation volume on initial echocardiography, aortic regurgitation was classified as mild, moderate, or severe.
To evaluate aortic dilatation in each patient, we measured the maximal dimension at each level of the aorta using computed tomographic angiography. The diameter of the aorta was measured at the annulus, sinus of Valsalva, sinotubular junction, mid aortic arch, upper descending thoracic aorta at the level just distal to the aortic arch, mid descending thoracic aorta at the level of pulmonary artery bifurcation, lower descending thoracic aorta at the level of left atrium, abdominal aorta at the level of renal artery, and lower abdominal aorta at the level of periumbilicus. Aortic diameter perpendicular to the aortic centerline axis at each level in the axial or coronal plane was defined as the maximal dimension.
In-hospital complications included ischemic events in multiple organ systems, development of hypotension, and cardiac tamponade. Adverse events were defined as death, reoperation for recurrent dissection or aneurysmal changes in the dissected aorta, and the progression of aortic dilatation by >1 cm at any part of the previously dissected aorta compared to most recent follow-up computed tomographic imaging. We also analyzed risk factors for these adverse events. The local institutional review board approved this observational study and waived the requirement for informed consent.
Continuous variables are expressed as the mean ± SD or as medians and interquartile ranges. To evaluate differences between groups, we used Student’s unpaired t test for normally distributed data and Mann-Whitney U tests for data not normally distributed. Categorical variables were compared using chi-square tests or Fisher’s exact tests. Event-free survival curves were constructed using the Kaplan-Meier estimator and compared using log-rank tests. The risks for each outcome were compared using Cox regression models. Calculations were performed using SAS version 9.1.3 (SAS Institute Inc., Cary, North Carolina). A p value <0.05 was considered significant.
Results
Of the 445 patients with aortic dissection, 46 (10%) had the MFS. The demographics and medical histories of patients with and those without the MFS who had aortic dissection are listed in Table 1 . Compared to patients without the MFS, patients with aortic dissection and the MFS were significantly younger (33 ± 10 vs 57 ± 13 years, p <0.001). Preexisting hypertension was less common in patients with the MFS than in those without the MFS (11% vs 73%, p <0.001). Presenting systolic and diastolic blood pressures were significantly lower in patients with the MFS. The initial symptoms of aortic dissection in the 2 groups were similar, and chest pain was predominant. At the time of initial presentation, patients with aortic dissection and the MFS had a statistically higher prevalence of aortic regurgitation (70% vs 44%, p = 0.028).
| Variable | MFS | p Value | |
|---|---|---|---|
| Yes (n = 46) | No (n = 399) | ||
| Age (years) | 33 ± 10 | 57 ± 13 | <0.001 |
| Men | 27 (59%) | 230 (58%) | 1 |
| Height (cm) | 180 (170–185) | 165 (157–172) | <0.001 |
| Body surface area (m 2 ) | 1.9 (1.7–2.0) | 1.7 (1.6–1.8) | <0.001 |
| Hypertension | 5 (11%) | 293 (73%) | <0.001 |
| Diabetes | 2 (5%) | 35 (9%) | 0.406 |
| Cerebrovascular accident | 1 (2%) | 27 (7%) | 0.34 |
| Chronic renal failure | — | 11 (3%) | 0.614 |
| Previous myocardial infarction | — | 7 (2%) | 1 |
| Bicuspid aortic valve | — | 7 (2%) | 1 |
| Presenting symptoms/signs | |||
| Asymptomatic presentation | 4 (9%) | 22 (6%) | 0.351 |
| Chest pain | 31 (67%) | 218 (55%) | 0.099 |
| Back pain | 6 (13%) | 83 (21%) | 0.213 |
| Abdominal pain | 2 (4%) | 39 (10%) | 0.291 |
| Dyspnea/syncope | 1 (2%) | 20 (5%) | 0.711 |
| Systolic blood pressure (mm Hg) | 119 (100–139) | 133.0 (114–156) | 0.001 |
| Diastolic blood pressure (mm Hg) | 55 (46–71) | 76.0 (60–90) | <0.001 |
| Echocardiographic findings | |||
| Aortic regurgitation | 32 (70%) | 176 (44%) | 0.028 |
| Mild | 12 (26%) | 138 (41%) | 0.036 |
| Moderate | 8 (17%) | 27 (8%) | 0.044 |
| Severe | 12 (2%) | 11 (3%) | <0.001 |
| Pericardial effusion | 8 (27%) | 162 (41%) | 0.009 |
| Pleural effusion | 6 (13%) | 136 (34%) | 0.004 |
The rate of acute presentation of aortic dissection was similar in the 2 groups (89% vs 82%, p = 0.223). Aortic dissection in patients with and without the MFS was characterized using computed tomographic imaging ( Table 2 ). Using the Stanford classification, the 2 groups did not differ in the prevalence of type A aortic dissection (67% vs 57%) or type B dissection (33% vs 43%) (p = 0.162). Involvement of the aortic root, including the annulus, sinus of Valsalva, and sinotubular junction as the origin of dissection, was nonsignificantly higher in patients with the MFS (32% vs 24%, p = 0.179). Of 46 patients with the MFS presenting with aortic dissection, none had a flap starting at the arch of aorta. The degree of flap extension was similar in the 2 groups, and this was also true for the lower abdominal aorta. Using measurements available, we compared the diameters at the widest point in each part of the aorta between groups. Patients with the MFS had significantly larger proximal aortic diameters than patients without the MFS, especially at the levels of the annulus, sinus of Valsalva, and sinotubular junction of the aorta. In contrast, aortic diameters from the ascending aorta to distal lower abdomen were larger in patients without the MFS. All of these findings were statistically significant. Patients without the MFS had more mural thrombus (52% vs 20%, p <0.001) and calcification (41% vs 20%, p = 0.005) of the aorta than those with the MFS.
| Variable | MFS | p Value | |
|---|---|---|---|
| Yes (n = 46) | No (n = 399) | ||
| Type A aortic dissection | 31 (67%) | 226 (57%) | 0.162 |
| Type B aortic dissection | 15 (33%) | 173 (43%) | — |
| Acute aortic dissection | 41 (89%) | 327 (82%) | 0.223 |
| Chronic aortic dissection | 5 (11%) | 72 (18%) | — |
| Site of aortic dissection origin | |||
| Aortic root | 17 (32%) | 97 (24%) | 0.179 |
| Ascending aorta | 19 (36%) | 146 (36%) | 1 |
| Aortic arch | — | 43 (11%) | 0.009 |
| Upper descending thoracic aorta | 6 (13%) | 80 (20%) | 0.731 |
| Mid descending thoracic aorta | 3 (7%) | 20 (5%) | 0.721 |
| Lower descending thoracic aorta | 1 (2%) | 12 (3%) | 1 |
| Upper abdominal aorta | — | 1 (0.3%) | 1 |
| Lower abdominal aorta | — | — | — |
| Flap extended to | |||
| Ascending aorta | 5 (10%) | 20 (5%) | 0.188 |
| Aortic arch | 2 (4%) | 18 (5%) | 1 |
| Upper descending thoracic aorta | — | 1 (0.3%) | 1 |
| Mid descending thoracic aorta | 3 (7%) | 22 (6%) | 0.734 |
| Lower descending thoracic aorta | 7 (15%) | 62 (16%) | 0.955 |
| Upper abdominal aorta | 1 (2%) | 36 (9%) | 0.157 |
| Lower abdominal aorta | 28 (61%) | 239 (60%) | 0.899 |
| Widest aortic dimension (mm) | |||
| Aortic annulus | 26.9 (23.4–29.8) | 23.5 (21.4–26.1) | 0.012 |
| Sinus of Valsalva | 52.8 (41.9–61.4) | 39.0 (35.8–43.0) | <0.001 |
| Sinotubular junction | 36.2 (29.6–53.8) | 29.9 (25.8–34.2) | <0.001 |
| Ascending aorta | 35.2 (31.3–40.6) | 41.0 (35.2–47.12) | <0.001 |
| Aortic arch | 31.1 (27.0–34.9) | 36.3 (32.4–40.8) | <0.001 |
| Upper descending thoracic aorta | 33.7 (29.2–39.3) | 37.7 (34.0–41.8) | 0.003 |
| Mid descending thoracic aorta | 31.2 (26.5–36.3) | 35.0 (31.7–39.4) | <0.001 |
| Lower descending thoracic aorta | 27.0 (24.5–33.4) | 33.2 (30.0–37.2) | <0.001 |
| Upper abdominal aorta | 23.3 (20.8–27.8) | 24.2 (21.8–27.1) | 0.857 |
| Lower abdominal aorta | 22.9 (20.7–27.3) | 22.4 (19.6–25.3) | 0.106 |
| Mural thrombosis of aorta | 9 (20%) | 208 (52%) | <0.001 |
| Calcification of aorta | 9 (20%) | 164 (41%) | 0.005 |
Management practices and complications of aortic dissection in patients with and without the MFS are listed in Table 3 . Patients with the MFS who experienced type B aortic dissection were more likely to undergo surgical treatment, although the rate of type B aortic dissection did not differ from that in patients without the MFS. In-hospital complications did not differ between groups, except for ischemic renal failure, which was more prevalent in patients without the MFS.
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