Aortic reoperation in a patient with Loeys-Dietz syndrome

Loeys-Dietz syndrome (LDS, OMIM #609192) is a recently recognized connective tissue disorder with clinical characteristics similar to Marfan syndrome. Aggressive aortic pathologies in LDS makes timely diagnosis and surgical intervention crucial compared to other genetic syndromes. We report a young man with LDS confirmed by genetic testing who twice underwent surgical operations to repair aortic aneurysm. In August 2000, a 14-year-old boy was admitted to our institute with significant aortic regurgitation. Preoperative echocardiogram revealed an aortic root aneurysm 5 cm in diameter and severe aortic insufficiency. He underwent composite graft replacement (Bentall procedure) with a 27 mm Medtronic Hall valved conduit (Medtronic, Inc., Minneapolis, MN, USA). He had an uneventful postoperative course and was discharged after nine days. The patient did not show up for the follow-up visits, and further evaluation of the aorta was not possible until he was re-admitted with tightness in the chest in November 2011 at the age of 25 years. Physical examination revealed a man of 183 cm height and 87 kg weight. He had variety of skeletal and craniofacial manifestations associated with LDS, including bifid uvula, high arch palate, mild hypertelorism, asymmetry pectus excavatum, thoracic scoliosis, pes planus, and horizontal striae on the lower back. Echocardiogram demonstrated no aortic regurgitation. There was trivial aortic stenosis with a maximum instantaneous gradient across the prosthetic aortic valve of approximately 20–25 mmHg. Magnetic resonance angiography (MRA) of the head showed extreme tortuosity of the left vertebral artery, which extended across the midline to the right causing indentation of the pontomedullary junction. There was tortuosity of the cavernous and supraclinoid segments of the internal carotid arteries bilaterally. Chest MRA demonstrated that the diameter of ascending aortic aneurysm and aortic arch aneurysm had enlarged to 8.9 cm in diameter. Family history included a sudden death of his mother. An aortic reoperation was performed via median resternotomy. On cardiopulmonary bypass, by cannulating the right femoral artery and vein, the ascending aorta and hemi-arch aneurysm was replaced with a 30 mm Gelweave tube graft (Vascutek Inc., Ann Arbor, MI, USA). He was discharged uneventfully on the 12th postoperative day. His maintenance medications included coumadin, metoprolol and angiotensin receptor blockade. Restrictions were instituted regarding vigorous physical activity, contact sports, and stimulant use. Molecular genetic testing subsequently showed an Arg487Gln mutation in exon 9 of the TGFBR1 gene (p. Arg487Gln), supporting a diagnosis of LDS type I. At six-month follow-up, abdominal MRA showed a diffuse fusiform aneurysm measuring 2.7 cm × 2.4 cm in the left common iliac artery. He is currently back to his regular work and doing well both clinically and hemodynamically 23 months postoperative. At his latest visit in July 2013, the chest and abdomen computed tomography angiogram (CTA) revealed left common iliac artery ectasia measuring approximately 5.2 cm × 2.6 cm that would require continued monitoring with either MRA or CTA. LDS is an autosomal dominant inherited disease associated with mutations of the transforming growth factorbeta receptor (TGFBR) 1 or TGFBR 2.1 The disease is characterized by the triad of hypertelorism, bifid uvula or cleft palate, arterial tortuosity and aortic aneurysms.2 Two subtypes of LDS have been defined based on craniofacial involvement.2 Patients with arterial aneurysms and tortuosity in the presence of craniofacial features such as craniosynostosis, hypertelorism, bifid uvula or cleft palate have been subtyped as LDS I. LDS II patients lack severe craniofacial features but have cutaneous findings similar to vascular type Ehlers-Danlos syndrome (vEDS).2 The diagnosis is suggested by typical clinical features but confirmed by genetic testing of the TGFBR1 or TGFBR 2. In this case, genetic DNA sequence analysis of the coding regions and splice sites of FBN1 (the gene that codes for fibrillin is responsible for MFS), TGFBR1 and TGFBR2 was performed. A mutation in the TGFBR1 gene was found that is thought to be consistent with LDS.Figure 1.: The imaging findings of a Loeys-Dietz patient who underwent the aortic reoperation. A and B: Pre-operative computed tomography angiogram demonstrating a huge aortic aneurysm measuring 8.9 cm in diameter. C and D: Post-operative computed tomography angiogram, the axial and coronal view, shows resection of the aneurysm and implantation of the graft. E: Follow-up volume rendered computed tomography imaging 20 months postoperative demonstrates significant improvement of the ascending aorta and the arch. Note the left common iliac artery ectasia measuring approximately 5.2 cm × 2.6 cm requiring continued monitoring.In comparison to Marfan syndrome, the nature of the aortopathy in LDS is even more aggressive, with a high risk of aortic dissection or rupture occurring at a younger age (the mean age of death is 26.0 years in LDS) and smaller diameters (even less than 4 cm in LDS).3 On the other hand, surgical mortality of vascular operation in LDS patients is reported to be less than 5% compared with 45% in patients with vEDS.3,4 Thus, it is important to distinguish LDS from Marfan syndrome and vEDS. Aggressive surgical intervention becomes the advocated treatment when LDS is identified. In view of the aggressive natural history of the associated aortopathy, multi-specialty consensus guidelines published in 2010 have recommended that MRA from the cerebrovascular circulation to the pelvis should be performed yearly in all patients with LDS. Surgical repair should be considered in all adult LDS patients with an aortic root diameter of 4.2 cm or greater by transoesophageal echocardiogram or 4.4 to 4.6 cm or greater by CTA and/or MRA (Class IIa, Level C).5 Betablockade and/or angiotensin receptor blockade can be used to prevent progression of aortic aneurysms and dissection. Although 25% of patients have a relevant family history, genetic testing and counseling for all family members is also recommended. It is the case of a confirmed LDS patient who has undergone aortic surgery twice to treat aortic aneurysm in China. The huge aortic aneurysm presented in our case highlights the need for short-interval follow-up imaging and aggressive surgical intervention in LDS. In conclusion, cardiac surgeons should be aware that Loeys-Dietz syndrome carries a worse prognosis than similar connective tissue disorders. All patients with LDS require strict control over blood pressure, rigorous imaging surveillance, followed by aggressive even prophylactic surgical treatment of identified vascular lesions.