Successful Coronary Artery Bypass in Ehlers-Danlos Type IV Syndrome Case Report and Review of the Literature

Abstract

Atherosclerotic coronary artery occlusive disease is very rare in cases of Ehlers-Danlos type IV syndrome. We report what we believe is a unique case of successful coronary artery bypass grafting for atherosclerotic coronary artery disease in a patient with this syndrome and examine the possible implications for the natural progression of the disease through a review of the literature. Nevertheless, we reiterate previous investigators' advice that any invasive procedure on these patients should be approached with extreme caution and that surgery should be performed as a last resort, considering the significantly elevated risks.

Atherosclerotic coronary artery occlusive disease is very rare in cases of Ehlers-Danlos type IV syndrome. We report what we believe is a unique case of successful coronary artery bypass grafting (CABG) for atherosclerotic coronary artery disease in an Ehlers-Danlos IV patient and examine the possible implications for the natural progression of Ehlers-Danlos IV—also called vascular Ehlers-Danlos syndrome (v-EDS)—through a review of the literature.

Case Report

In June 2004, a 28-year-old man presented at a local hospital with acute onset of chest pain and electrocardiographic changes in the anterolateral leads. His family history was notable for the fatal rupture of an aortic aneurysm in a brother. There were no significant risk factors for atherosclerosis except for active cigarette smoking. Because ascending aortic dissection was suspected upon initial computed tomographic (CT) angiography of the chest, the referring hospital transferred him to our institution for further management.

Repetition of chest CT angiography ruled out aortic dissection, but emergent cardiac catheterization revealed significant single-vessel coronary artery occlusive disease involving the left anterior descending coronary artery (LAD). Two bare-metal coronary stents were deployed without incident. The patient had an uneventful recovery and was discharged from the hospital on β-blockade, angiotensin-converting enzyme inhibitor, and dual antiplatelet therapy. About 1 month later, the patient experienced recurrent angina. Cardiac catheterization revealed patent stents and a localized LAD dissection distal to the stents. The patient was maintained on medical therapy, and this was followed by improvement of his symptoms.

Four months later, the patient presented at our emergency department with an acute anterior ST-elevation myocardial infarction. Emergent cardiac catheterization (Fig. 1) revealed an 80% obstructive atherosclerotic lesion of the LAD, aneurysmal dilation of the LAD, and a new area of LAD dissection, all distal to the stents (Fig. 2). The patient was maintained on medical therapy in preparation for surgical coronary revascularization.

Fig. 1 Still image from cardiac catheterization study shows the atherosclerotic lesion distal to the stent and the aneurysmal dilation of the left anterior descending coronary artery.

Fig. 2 Line drawing shows the results of cardiac catheterization before surgical intervention.

LAD = left anterior descending coronary artery; LCx = left circumflex coronary artery; LMCA = left main coronary artery

During surgery, the harvested left internal thoracic artery (LITA) was noted to have a spontaneous dissection at its distal segment; this was excised, and the rest of the artery was found suitable for grafting. Off-pump CABG using the LITA to the LAD was performed, with proximal and distal ligation of the aneurysmal LAD segment. The postoperative course was uneventful, and the patient remained symptom-free after 3 years' follow-up.

The patient was referred to the regional genetics clinic, where he was confirmed to have Ehlers-Danlos IV.^* Earlier testing had confirmed the presence of the disease in several members of his family.¹

Discussion

The clinical presentation of abnormal connective tissue was described as early as 400 BC by Hippocrates.² In 1899 and 1908, Edvard Ehlers and Henri Alexandre Danlos, respectively, presented a clinical syndrome of skin laxity, joint subluxation, and easy bruising to the Paris Society of Syphilology and Dermatology.^3,4 The heterogeneous group of diseases known as Ehlers-Danlos syndrome comprises a variety of inherited connective-tissue disorders characterized by articular hypermobility, skin laxity and extensibility, and tissue fragility particularly affecting vascular structures. Seven types of EDS have been recognized,^4–6 of which type IV, the vascular or arterial-ecchymotic type, is relevant to this discussion. It is the result of a mutation of the COL3A1 gene, which leads to disruption of the synthesis and polymerization of the collagen α-1(III) chain. Vascular EDS is characterized by arterial fragility, a higher rate of aneurysm formation, and premature death due to spontaneous arterial, intestinal, or uterine rupture. About 80% of patients with v-EDS experience at least one complication by age 40, particularly arterial rupture or dissection. Because of the severe tissue fragility and tendency toward spontaneous rupture, surgical and other invasive interventions have usually been discouraged. Even arteriography is to be avoided.^7–12

Because of its origin and clinical features, Ehlers-Danlos IV has been included in the recently designated Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC) national registry, which also includes Marfan syndrome, Loeys–Dietz syndrome, and others. Recent evidence suggests a role for transforming growth factor β-1 in triggering a signaling cascade that affects several types of matrix metalloproteinases (MMP-2, MMP-9, and MMP-12) and tissue inhibitors of metalloproteinases (TIMP1–3)—resulting in increased proteolysis in the aortic wall, decreased structural integrity, and increased prevalence of aneurysms, dissections, and spontaneous ruptures. This is in contrast to the pathways of atherosclerotic phenomena involving specific mediators of inflammatory response—for example, interleukin-1β, tumor necrosis factor-α, interferon-γ, C-reactive protein, and Vascular Adhesion Protein-1 (VAP-1).¹³

The paucity of atherosclerotic or atherothrombotic processes (coronary artery disease resulting in myocardial infarction and calcific aortic valve disease) is another characteristic feature of these conditions. Our review of the literature has shown only a few cases of atherosclerotic coronary artery disease that resulted in myocardial infarction^14–16 and one case of valve replacement for calcific aortic stenosis.¹⁷ Coronary artery involvement (see Table I)12,14–16,18–20 is attributable predominantly to aneurysmal formation.^19,20 We found only one case in which CABG had been performed, using a vein conduit.¹⁸ The small number of surgical procedures reported in this patient population is indicative of the high risk of surgery, particularly when it involves vascular structures. As with other members of the GenTAC group, this condition presents significant challenges to the surgeon, especially in harvesting arterial conduits, cannulation, cross-clamping, performing vascular anastomoses, and arterial repair and hemostasis.^21–24

TABLE I. Summary of Reports of Coronary Artery Involvement in Ehlers-Danlos Syndrome Type IV

In conclusion, we believe that we are reporting the first case of successful CABG with use of an arterial conduit in a patient with Ehlers-Danlos type IV syndrome. We reiterate previous investigators' advice that any invasive procedure on these patients should be approached with extreme caution and that surgery should be performed as a last resort, considering the significantly elevated risks.