Prospective Cardiovascular Genetics Evaluation in Spontaneous Coronary Artery Dissection

Abstract

Background: Previous studies describing genetics evaluation in spontaneous coronary artery dissection (SCAD) have been retrospective in nature or presented as single case reports. As part of a dedicated clinical program, we evaluated patients in cardiovascular genetics clinic to determine the role of genetically triggered vascular disease and genetic testing in SCAD. Methods and Results: Patient data were entered prospectively into the Massachusetts General Hospital SCAD registry database from July 2013 to September 2017. Clinically indicated genetic testing was conducted based on patient imaging, family history, physical examination, and patient preference. Of the 107 patients enrolled in the registry, 73 underwent cardiovascular genetics evaluation at our center (average age, 45.3±9.4 years; 85.3% female), and genetic testing was performed for 44 patients. A family history of aneurysm or dissection was not a prevalent feature in the study population, and only 1 patient had a family history of SCAD. Six patients (8.2%) had identifiable genetically triggered vascular disease: 3 with vascular Ehlers–Danlos syndrome ( COL3A1 ), 1 with Nail–patella syndrome ( LMX1B ), 1 with autosomal dominant polycystic kidney disease ( PKD1 ), and 1 with Loeys–Dietz syndrome ( SMAD3 ). None of these 6 had radiographic evidence of fibromuscular dysplasia. Conclusions: In this series, 8.2% of the SCAD patients evaluated had a molecularly identifiable disorder associated with vascular disease. The most common diagnosis was vascular Ehlers–Danlos syndrome. Patients with positive gene testing were significantly younger at the time of their first SCAD event. A low threshold for genetic testing should be considered in patients with SCAD.

Features of Marfan syndrome not listed in the Ghent nosology – the dark side of the disease

“…In a study of 114 cases of SCAD retrospectively evaluating for connective tissue disease, 3 were diagnosed with connective tissue disease, including 1 with Marfan syndrome and 2 with vascular Ehlers-Danlos syndrome [82]. Another study of 107 patients with SCAD were prospectively considered for genetic evaluation [93]. Among this group, no patients with Marfan syndrome were detected, but 3 with COL3A1 variants and 1 with a SMAD3 variant were diagnosed.…”

Spontaneous coronary artery dissection: contemporary aspects of diagnosis and patient management

“…Coexisting autoimmune or connective tissue disorders such as systemic lupus erythematosus, polyarteritis nodosa, inflammatory bowel disease, polycystic kidney disease, Ehlers-Danlos or Marfan-like syndromes have been also highlighted as potential predisposing/precipitating factors for SCAD 44–52. Nevertheless, this relation is mainly described in case reports, as cohort studies data do not suggest a strong association: 0%–8% for connective tissue disorders2 8 9 53 54 and 0%–12% for autoimmune or inflammatory disorders 1 8 9. And yet, the coexistence of any of these conditions may be relevant at the level of individual patients presenting with SCAD, thus screening for symptoms and syndromic features has been recommended 14.…”

“…A marginal number (~1%) of SCAD cases have been shown to present familiar aggregation 68. For the time being, the only genetic findings are related to connective tissue disorders52–54 and represent a minority of the cases. Although research is hampered by the rarity of the condition, genetic data collection should be sought for collaborative studies.…”

Update in Spontaneous Coronary Artery Dissection

“…Genetic testing of patients diagnosed with SCAD without FMD is being offered at Massachusetts General Hospital, where a panel of molecular genetic tests have identified a pathologic gene mutation in COL3A1, a causative gene in vascular Ehler–Danlos as present in 4.1% of the SCAD population at their tertiary referral center [ 36 ]. Other genes have been identified including the F11R gene which encodes for the F11 receptor, a junctional adhesion molecule A, that concerns the regulation of tight junction assembly in endothelial cells [ 37 ].…”