Spontaneous Coronary Artery Dissection in Loeys-Dietz Syndrome: Role of Optical Coherence Tomography in Diagnosis and Management

Abstract: Coronary artery aneurysm with dissection is an uncommon presentation of Loeys-Dietz syndrome (LDS). Diagnosis and management of patients with LDS who present with unstable clinical syndromes merit special attention given unique pathophysiology derangements associated with this disease entity. Clinical experience in treating such patients is limited to a few case reports, and an optimal catheter-based treatment approach is less well defined. Intravascular imaging techniques, particularly optical coherence tomography (OCT), are able to provide further insight about the morphology of lesions and guide-catheter based intervention. In this case report, we describe one such patient and highlight the key morphological characteristics of coronary artery disease in patients with LDS as well as the crucial role of OCT in its management. 

J INVASIVE CARDIOL 2015;27(9):E196-E198

Key words: cardiac imaging, Loeys-Dietz syndrome, optical coherence tomography

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Loeys-Dietz syndrome (LDS) is a recently described connective tissue disorder characterized by generalized arterial tortuosity and aneurysms¹ most commonly involving the aortic root. Although aneurysmal events have been reported in all aortic segments and its branches including the subclavian, renal, superior mesenteric, hepatic, and arteries of the head and neck,¹ coronary involvement in LDS is rare. We describe a patient with LDS presenting with an acute coronary syndrome where angiography and intravascular imaging played a critical role in understanding and further management of the clinical syndrome.

Case #1

A 55-year-old man with LDS presented to our emergency room with chest pain. Three years ago, he underwent descending and ascending valve sparing aortic replacement surgery. At that time, he was diagnosed with LDS with typical clinical features including bilateral club foot, pectus-carinatum, esophageal spasm and stricture, bifid uvula, malar hypoplasia, soft velvety skin, and a positive finding for the TGF-b receptor 1 (TGFBR-1) gene mutation. There was no prior history of a familial aneurysmal syndrome, but his son subsequently tested positive for the TGFBR-1 gene mutation. His past history included hypertension, tobacco use, and obstructive sleep apnea, but he had no other cardiovascular risk factors. On presentation, he was taking losartan and nebivolol. 

On the day of admission, he presented with substernal chest pain beginning at rest, radiating to his jaw and lasting 30 minutes. His admission electrocardiogram (ECG) demonstrated sinus bradycardia with no ST or T-wave changes. Cardiac biomarkers and serial ECGs were unrevealing for acute ischemia, but pharmacologic nuclear stress testing was notable for reversible ischemia. Coronary angiography via the left radial artery demonstrated an eccentric, discrete 70% lesion involving the proximal left anterior descending (LAD) artery, at the origin of the first diagonal branch. Linear dye penetration into the vessel wall was noted, suggesting an ulcerated lesion or focal dissection (Figure 1A). The left main artery was noted to be ectatic, but the rest of the coronary anatomy demonstrated minimal luminal irregularities. After crossing the lesion with a standard coronary guidewire, optical coherence tomography (OCT) imaging (C7 Dragonfly catheter; St. Jude Medical) was performed to define morphologic features of the lesion, revealing a focal out-pouching of the vessel with a disrupted edge, consistent with dissection with evidence of residual acute (red) thrombus at the lumen border (Figures 1B and 1C). The vessel at the most stenotic site was noted to consist of mixed fibrotic and lipid plaque with a minimal lumen diameter of 1.99 mm and minimal luminal area of 4.34 mm². The lumen dimensions by OCT in the region proximal and distal to the dissection were not noted to be aneurysmal, with minimal lumen diameter of 3.24 mm and a minimal lumen area of 8.24 mm² at the proximal reference segment. The 14.2 mm-long lesion was approached by stenting with a 3.25 x 18 mm everolimus-eluting stent, followed by postdilatation with excellent angiographic results and no evidence of residual dissection (Figure 2B). Post-stent OCT imaging demonstrated no evidence of stent malapposition, and no uncovered dissection flap (Figure 2C). The patient was discharged uneventfully, without further symptoms. Six months later, coronary angiography was repeated as part of an atypical chest pain evaluation demonstrating no evidence of recurrent or residual coronary dissection and a widely patent stent (Figure 2D).

Discussion

LDS is a recently described autosomal dominant connective tissue disorder caused by heterozygous mutation of the gene encoding for TGFBR-1. It is characterized by aggressive vascular involvement, generalized arterial tortuosity, bifid uvula/cleft palate, hypertelorism, craniosynostosis, translucent skin, and cervical spine malformations.¹ As a result of a severe defect in elastogenesis, the risk of arterial dissection or rupture in LDS patients is believed to be high even at dimensions that normally are not predictive of such events. Congenital cardiac defects associated with LDS include atrial septal defect, bicuspid aortic or pulmonary valves, and mitral valve prolapse. Although the thoracic aorta is involved most frequently, aneurysms and dissections in almost every aortic branch have been reported.¹ Coronary artery involvement appears to be less frequent, with experience limited to isolated case reports. Coronary aneurysm, dissection, and stenoses have also been reported following ascending aortic repair in LDS patients.^2,3 Much less is known about management options in this patient population. Our patient was successfully treated with an intracoronary stent, with no signs of disease recurrence on follow-up angiography. Fattori et al⁴ described a similar case of coronary artery dissection treated successfully with intracoronary stents. 

Coronary artery dissection leads to formation of a false lumen, which may cause arterial lumen compromise, particularly if there is hematoma formation. Routine angiographic assessment in such situations is marked by significant false-positive and false-negative results. This poses unique challenges during percutaneous coronary intervention (PCI), where identification of the true arterial lumen or proper intracoronary guidewire placement is crucial. OCT provides high-resolution intraluminal images, and therefore can aid in diagnosis and guide management strategies in such cases. In our patient, OCT was valuable in establishing the diagnosis of coronary dissection by visualization of the dissection flap and excluding an aneurysm or ulceration. In addition, OCT demonstrated the exact location and arc of disrupted intimal layers, allowed differentiation of true and false lumen, and verified optimal placement of the intracoronary wire in the true lumen. Successful outcome of a PCI for dissection requires accurate assessment of lesion dimensions for optimal stent sizing, successful sealing of the subintimal entry site, and in some cases covering the entire dissected segment. Furthermore, OCT imaging of our patient aided in explaining the mechanism of coronary ischemia in the setting of a non-obstructive plaque by demonstrating vessel disruption, dissection, and the presence of residual thrombus. 

Conclusion

In summary, we present a case of an OCT-guided percutaneous intervention in a patient with LDS who presented with spontaneous coronary artery dissection, highlighting the value of intracoronary imaging for diagnosis of coronary artery disease (and more specifically, coronary dissection) in this syndrome. Moreover, this case emphasizes the importance of considering myocardial ischemia as a source of chest pain in patients with LDS or other connective tissue disorders.

References

1. Loeys BL, Dietz HC. Loeys-Dietz syndrome. GeneReviews (NCBI Bookshelf), available at www.ncbi.nlm.nih.gov/books/NBK1116. University of Washington, Seattle; February 28, 2008.
2. Kato Y, Hattori K, Motoki M, Takahashi Y, Nishimura S, Shibata T. Left coronary ostial stenosis after the modified bentall using a long interposed coronary graft in a patient with pectus excavatum. Ann Thorac Cardiovasc Surg. 2014;20(Suppl):758-760. Epub 2013 Feb 28.
3. 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:S757-S763.
4. Fattori R, Sangiorgio P, Mariucci E, et al. Spontaneous coronary artery dissection in a young woman with Loeys-Dietz syndrome. Am J Med Genet A. 2012;158A:1216-1218.

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From the ¹Cardiovascular Division, Department of Internal Medicine, Loyola University Medical Center, Maywood, Illinois; ²Loyola University Hospital, Stritch School of Medicine, Chicago, Illinois; and ³Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Illinois.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lopez reports research grants and consultant fees from St. Jude Medical. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted September 4, 2014, final version accepted September 17, 2014.

Address for correspondence: Anoop Agrawal, MD, Cardiovascular Division EMS Bldg, 6th Floor, 2160 S. 1st Avenue, Maywood, IL 60153. Email: anoopaiims@gmail.com