Ann Thorac Surg 2009;87:1949-1951. doi:10.1016/j.athoracsur.2008.10.049
© 2009 The Society of Thoracic Surgeons
Case Reports
Total Aortic Replacement in Loeys-Dietz Syndrome
J. Scott Rankin, MDa,
Alan C. Braverman, MDb,
Nicholas T. Kouchoukos, MDc,*
a Centennial Medical Center and Vanderbilt University, Nashville, Tennessee
b Washington University School of Medicine, St. Louis, Missouri
c Missouri Baptist Medical Center, St. Louis, Missouri
Accepted for publication October 21, 2008.
* Address correspondence to Dr Kouchoukos, 3009 N Ballas Rd, Suite 360C, St. Louis, MO 63131 (Email: ntkouch{at}aol.com).
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Abstract
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Loeys-Dietz syndrome presents early in life with rapidly progressive aortic aneurysmal disease, hypertelorism, and bifid uvula/cleft palate. Genetic testing reveals transforming growth factor-β 1 and 2 mutations. Patients require monitoring for progressive aneurysmal disease, and may need total aortic replacement. Two patients are presented who typify these concepts.
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Introduction
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Inherited connective tissue disorders are associated with aortic aneurysms and dissections. Marfan syndrome is an example, in which mutation of the FBN1 gene encoding the protein fibrillin-1 causes the associated defects [1]. Recently, another genetic complex, Loeys-Dietz syndrome (LDS), has been described, and is characterized by rapidly progressive and generalized aortic and branch vessel disease, hypertelorism, and bifid uvula/cleft palate [2]. Loeys-Dietz syndrome carries a worse prognosis than Marfan syndrome, with an average age for aortic surgery of 17 years and a life expectancy of 23 years in the earliest series [2]. Thus, a better understanding of LDS and its clinical implications is important. In this report, two patients are described who exhibited clinical characteristics of LDS and required extensive staged replacement of the aorta at a young age.
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Case Reports
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Patient 1
In 2006, a 22-year-old woman experienced an acute type A aortic dissection diagnosed by computed tomography (CT) scanning, likely superimposed on a preexisting aortic root aneurysm (Fig 1). She had a history of bilateral club foot repair and was considered to have vascular Ehlers-Danlos syndrome, but this had not been confirmed by genetic testing. Pectus carinatum was noted on examination, and she was hemodynamically stable. She underwent emergency aortic root replacement using a valve-graft conduit. Recovery was uneventful, and a predischarge CT scan showed satisfactory appearance of the conduit and a 3.5-cm diameter patent distal aortic false lumen extending into the abdomen. She was placed on a regimen of beta-blocker and antihypertensive therapy and scheduled for follow-up CT examination in 6 months.
Three months postoperatively, the patient complained of vague back pain, and a CT scan showed that the entire patent distal false lumen, from the aortic arch to the iliac bifurcation, had enlarged, with a maximum diameter of 6 cm in the descending aorta. She underwent graft replacement of the remaining thoracic aorta to the level of the T-9 intercostal arteries using a clam shell approach and profound hypothermia [3]. The proximal anastomosis was to the valve-graft conduit, the brachiocephalic vessels were attached with separate grafts, and the distal aorta was fenestrated to permit perfusion of both lumens. She recovered uneventfully, and CT imaging showed a satisfactory result. She was scheduled for further evaluation of the remaining aorta in 3 months.
Within 1 month, the patient complained of lower back pain, and CT imaging showed continued expansion of the false lumen. She was readmitted, and underwent replacement of the remaining thoracic and the entire abdominal aorta using a retroperitoneal flank incision and profound hypothermia [4]. Three pairs of distal intercostal arteries were reimplanted into the graft, and the visceral and renal arteries were revascularized with individual branch grafts. Recovery was uneventful, and postoperative imaging was satisfactory. Subsequent physical examination identified a bifid uvula, and genetic testing revealed a transforming growth factor (TGF)-β 2 mutation, confirming the diagnosis of LDS. The patient continues to do well 1 year postoperatively, and has returned to college to pursue a medical career.
Patient 2
In 1995, a 15-year-old girl underwent aortic root replacement for an aortic root aneurysm using a valve-graft conduit, and was thought to have Marfan syndrome. In 2004, aneurysmal dilation of her distal ascending aorta, arch, and proximal descending aorta developed. She underwent single-stage replacement of these segments using a clam shell incision and profound hypothermia. In 2006, a large aneurysm of the remaining descending aorta developed, and she underwent replacement to the level of the T-10 intercostal arteries using profound hypothermia and circulatory arrest. Her recovery was uncomplicated, and she remains well on a regimen of beta-blocker therapy. Genetic testing revealed a TGF-β 1 mutation, confirming the diagnosis of LDS. The patient is being followed with CT scans every 6 months to monitor the remaining aorta.
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Comment
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Based on clinical experience, it has been suggested that variants of genetic aneurysmal disease similar to but distinct from Marfan syndrome exist [5]. Recently, several genetic mutations have been shown to account for a variety of aneurysmal disorders. While several, such as bicuspid aortic valve disease [6] and familial thoracic aortic aneurysm and dissection syndromes [7], are continuing to be characterized, LDS is known to be caused by mutations in the TGF-β receptor [2]. Mutations in this receptor increase downstream signaling of the cytokine TGF-β in blood vessels, leading to overproduction of collagen, loss of elastin content, and disarray of elastic fibers. These patients often carry alternative diagnoses initially, as ours did. When compared with Marfan syndrome, the vascular disease in LDS tends to be generalized and has an especially malignant natural history. Many patients present in childhood or young adulthood [8, 9]. Rupture can occur at an early age or at aortic diameters that ordinarily would not be predictive of this complication. Once the diagnosis is made, frequent aortic imaging is indicated, and aneurysmal progression may be especially rapid after aortic dissection, as occurred in our first patient. Staged replacement of affected aortic segments is indicated, sometimes leading to replacement of the entire aorta, as in patient 1. Because the disorder is autosomal dominant with variable clinical expression, genetic counseling and screening of family members is recommended.
Total aortic replacement is a major surgical procedure that has carried significant mortality and morbidity in the past. Recent advances in intraoperative management have greatly improved outcomes [3, 4]. Profound hypothermia is ideal for organ protection, not only for the brain but also for the spinal chord and abdominal organs. Continuous perfusion of the cerebral vasculature through axillary artery cannulation during arch replacement has minimized the duration of circulatory arrest, and greatly reduced the incidence of neurologic injury [3]. Hypothermic protection of the spinal cord, together with routine reimplantation of distal thoracic intercostal/lumbar arteries, has been associated with a low incidence of paraplegia [4]. Likewise, hypothermic protection of the kidneys and abdominal viscera has reduced the incidence of organ failure. The clam shell incision has allowed larger segments of aorta to be replaced in a single stage, thus reducing the number of operations required.
In summary, LDS is caused by mutations in the TGF-β receptor 1 and 2 genes, and is characterized by progressive aortic aneurysmal disease and dissection. Patients present at an early age and require vigilant monitoring of all vascular segments because of the rapidly progressive nature of the aortic disease. Surgical management using new supportive strategies is likely to produce better long-term outcomes, and total aortic replacement may be necessary.
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References
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- Dietz HC, Cutting G, Pyeritz R, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene Nature 1991;352:337-339.[Medline]
- Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-β receptor N Engl J Med 2006;355:788-798.[Medline]
- Kouchoukos NT, Mauney MC, Masetti P, et al. Single-stage repair of extensive thoracic aortic aneurysms: experience with the arch-first technique and bilateral anterior thoracotomy J Thorac Cardiovasc Surg 2004;128:669-676.[Abstract/Free Full Text]
- Kouchoukos NT, Masetti P, Rokkas CK, et al. Hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta Ann Thorac Surg 2002;74(Suppl):1885-1887.
- Wolfe WG, Oldham HN, Rankin JS, et al. Surgical treatment of acute ascending aortic dissection Ann Surg 1983;197:738-742.[Medline]
- Braverman AC, Guven H, Beardslee MA, et al. The bicuspid aortic valve Curr Prob Cardiol 2005;30:461-522.
- Pannu H, Avidan N, Tran-Fadulu V, Milewicz DM. Genetic basis of thoracic aortic aneurysms and dissections: potential relevance to abdominal aortic aneurysms Ann NY Acad Sci 2006;1085:242-255.[Medline]
- Williams JA, Loeys BL, Nwakanma LU, et al. Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease Ann Thorac Surg 2007;83(Suppl):757-763.
- Lee RS, Fazel S, Schwarze U, et al. Rapid aneurysmal degeneration of a Stanford type B aortic dissection in a patient with Loeys-Dietz syndrome J Thorac Cardiovasc Surg 2007;134:242-243.[Free Full Text]
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Abstract
Introduction
