Loeys-Dietz syndrome (LDS) is a recently described connective tissue disorder characterized by early and aggressive onset of aneurysm formation and dissection of the aorta.[1] The lesions in these patients present early, often in childhood, and at much smaller aortic diameters.[2] Mean age of survival for patients diagnosed with LDS is 37 years.[3] These patients also have a typical phenotype: including a bifid uvula, hypertelorism, cleft palate, and vascular tortuosity derived from genetic alterations in TGF β.[1, 3] Specifically, management of thoracic vascular abnormalities drives the treatment of these patients. We describe a patient with LDS who presented with multiple aortic aneurysms, cerebral aneurysms and surprisingly, concomitant coronary artery disease.

A 52-year-old man presented to the emergency room with lower back pain. He had strained his back a few months previously and the pain never resolved. He eventually underwent an MRI and was found to have an eight centimeter abdominal aortic aneurysm. He was referred for aortic consultation and after further questioning, was found to have a significant family history. His brother had previously undergone successful valve sparing aortic root replacement and was diagnosed with LDS. Our patient had refused both genetic testing and imaging at the time of his brother’s diagnosis. After genetic testing, he was found to have the TGFBR1 mutation, which was the same mutation as his brother, and the diagnosis of LDS was made. He underwent further imaging studies and was found to have a 5 cm aortic root aneurysm, 8 cm infra-renal aortic aneurysm, 7mm left cavernous internal carotid artery aneurysm and a 7 mm basilar artery aneurysm [Figure 1]. Because of size and symptoms, plans were made for initial abdominal aortic aneurysm repair, followed by subsequent aortic root replacement. He underwent successful open aorto-bi-iliac infra-renal aneurysm repair.

Figure 1: CTA imaging showing aortic root as well as abdominal aneurysms. (Arrows denote aneurysms.)

In preparation for his aortic root surgery, a cardiac catheterization was performed and a 75% stenosis of his proximal left anterior descending artery was found [Figure 2]. Echocardiogram confirmed the dilated aortic root and revealed a tricuspid aortic valve with mild aortic insufficiency.

Figure 2: LHC showing ostial stenosis of the left anterior descending coronary artery. (Arrow denotes stenotic lesion.)

After recovering from his abdominal aortic aneurysm repair, he underwent a valve sparing aortic root replacement with coronary artery bypass grafting. The aortic root was replaced with a Valsalva graft, the aortic valve spared and re-implanted in the fashion of a David IV procedure. The distal aortic (proximal to the innominate artery) and coronary button anastomoses were reinforced with Teflon felt. This was performed with standard cardiopulmonary bypass, distal aortic cross clamp and antegrade myocardial protection. The left anterior descending coronary artery was grafted using the left internal mammary artery, harvested in a pedicle fashion. The procedures and recovery were unremarkable. His one month follow-up echocardiogram showed no aortic insufficiency and his computed tomography scan showed intact aneurysm repairs. 

LDS is a connective tissue disorder first described by Loeys et al in 2005.[1] Similar to Marfan’s Syndrome, this disease is autosomal dominant and patients have a severe defect in elastogenesis as a result of a mutation in the TGFBR gene. It is well known for its aggressive vascular involvement, especially aortic dissections and aneurysms Because of the high risk of aortic dissections and aneurysmal disease, patients with LDS undergo intervention sooner than the average population.[2, 3] When one vascular defect is found, it is recommended that complete body imaging be done in order to evaluate for the presence of other aneurysmal disease. The life expectancy of these patients is decreased when compared with the general population. Typical of this disease, our patient was found to have multiple vascular aneurysms. Though not the oldest patient described with LDS, our patient is much older than average life expectancy and because of his relatively advanced age, we elected to perform a coronary angiogram. To our knowledge, this is the first described case of coronary artery disease in a patient with LDS. There have been previous descriptions of patients with dissections of the coronary arteries,[4, 5] but never with a stenotic lesion requiring intervention. The prevalence of coronary artery disease is unknown in patients with LDS, likely because most patients with this syndrome do not progress to an age when coronary angiography would be indicated. When evaluating surgical vascular disease in these complex connective tissue patients, concomitant coronary disease cannot be dismissed, and should be investigated in appropriate patients based on established clinical guidelines.

We present a patient with LDS who had concomitant coronary artery disease, highlighting the value of a thorough workup in patients with complicated connective tissue disorders. This emphasizes the need to consider routine cardiac diagnoses and appropriate workup for patients with such vascular diseases.

1. Loeys, B.L., et al., A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet, 2005. 37(3): p. 275-81.

2. Williams, J.A., et al., Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease. Ann Thorac Surg, 2007. 83(2): p. S757-63; discussion S785-90.

3. Loeys, B.L., et al., Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med, 2006. 355(8): p. 788-98.

4. Fattori, R., et al., Spontaneous coronary artery dissection in a young woman with Loeys-Dietz syndrome. Am J Med Genet A, 2012. 158a(5): p. 1216-8.

5. Agrawal, A., et al., Spontaneous Coronary Artery Dissection in Loeys-Dietz Syndrome: Role of Optical Coherence Tomography in Diagnosis and Management. J Invasive Cardiol, 2015. 27(9): p. E196-8.

The views expressed in this article are those of the authors and do not reflect the official policy of the United States Air Force, Department of Defense, or the U.S. Government.

Financial Disclosure: None.

Prior presentation: This work was not been previously presented in any format.