Fibrillar Collagen Variants in Spontaneous Coronary Artery Dissection.

IMPORTANCE: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute myocardial infarction enriched among individuals with early-onset myocardial infarction but is of unclear etiology. OBJECTIVE: To assess which genes contribute to the development of SCAD. DESIGN, SETTING, AND PARTICIPANTS: To prioritize genes influencing risk for SCAD, whole-exome sequencing was performed among individuals with SCAD in the discovery and replication cohorts from a tertiary care hospital outpatient specialty clinic, and gene set enrichment analyses were also performed for disruptive coding variants. All patients were sequentially enrolled beginning July 2013. Aggregate prevalence of rare disruptive variants for prioritized gene sets was compared between individuals with SCAD with population-based controls comprising 46 468 UK Biobank participants with whole-exome sequencing. Complementary mice models were used for in vivo validation. Analysis took place between June 2020 and January 2021. MAIN OUTCOMES AND MEASURES: The frequency and identity of rare genetic variants in individuals with SCAD. RESULTS: Of 130 patients, 109 (83.8%) were female (26 of 32 [81.2%] in the discovery cohort and 83 of 98 [84.7%] in the replication cohort) with mean (SD) age at first SCAD event of 48.41 (8.76) years in the discovery cohort and 47.74 (10.09) years in the replication cohort. Across all patients with SCAD, rare disruptive variants were found within 10 collagen genes (COL3A1, COL5A1, COL4A1, COL6A1, COL5A2, COL12A1, COL4A5, COL1A1, COL1A2, and COL27A1) were 17-fold (P = 1.5 × 10-9) enriched among individuals with SCAD compared with a background of 2506 constrained genes expressed in coronary artery. Furthermore, compared with individuals from the UK Biobank, individuals with SCAD were 1.75-fold (P = .04) more likely to carry disruptive rare variants within fibrillar collagen genes. Complementary mice models haploinsufficient for Col3a1 or Col5a1, the 2 most common collagen gene variants identified in SCAD cases, demonstrated increased risk of arterial dissection and increased size of arterial diameters especially in female mice, with resulting changes in collagen fibril organization and diameter. CONCLUSIONS AND RELEVANCE: Unbiased gene discovery in patients with SCAD with independent human and murine validation highlights the role of the extracellular matrix dysfunction in SCAD.

Management of spontaneous coronary artery dissection complicated by cardiogenic shock using mechanical circulatory support with the Impella device.

OBJECTIVE: The aim is to evaluate the feasibility of using mechanical circulatory support, specifically the Impella device, in spontaneous coronary artery dissection (SCAD) patients with cardiogenic shock. BACKGROUND: The therapeutic options for managing SCAD complicated by cardiogenic shock are limited. Risky revascularization procedures are often necessary. METHODS: This was a multicenter case series in the United States. Approximately 20 cases of Impella implantation in patients with SCAD are known. The implanting physician for each of these cases was contacted and de-identified records were requested. The records were analyzed for Impella indications, outcomes, and complications. RESULTS: Records from four cases were received. All patients survived to hospital discharge and no major complications were observed. In two cases, cardiogenic shock developed in the absence of ongoing ischemia, suggesting a Takotsubo-like cardiomyopathy. In these cases, the Impella provided hemodynamic support until the patient's cardiac function recovered. CONCLUSION: Although a small case series, given the scarcity of SCAD cases complicated by cardiogenic shock and the limited therapies available to treat these patients, these data are of clinical value in highlighting the feasibility of Impella use in SCAD. The Impella can be valuable for procedural support and in cardiogenic shock, especially in cases without evidence of ongoing ischemia.

Is it necessary to assess for fat-soluble vitamin deficiencies in pediatric patients with newly diagnosed celiac disease?

BACKGROUND: The purpose of this study was to identify the frequency of fat-soluble vitamin deficiencies in children with celiac disease (CD) and to determine the value of routine testing for these deficiencies. METHODS: We conducted a retrospective medical record review of patients with a confirmed diagnosis of CD and fat-soluble vitamin levels measured at diagnosis between 1995 and 2012 at Mayo Clinic. Patients' demographics, fat-soluble vitamin levels, and pertinent clinical factors at the time of diagnosis were collected. RESULTS: Eighty-three patients were included in the final analysis: 51 girls and 32 boys, with an average age at diagnosis of 12.8 years in girls and 13.0 years in boys. The most commonly reported symptoms were abdominal pain in 49 patients and diarrhea in 30 patients. Family history of CD was reported in 32 patients. Average vitamin levels for vitamin E, 25-hydroxyvitamin D (25 (OH) D), and vitamin A were 7.5 mg/L, 32.8 ng/mL, and 334.5 µg/dL, respectively. No patients had vitamin A deficiency, 2 patients had vitamin E deficiency, and 9 patients had mild-to-moderate vitamin D deficiency (none had severe deficiency). Both patients with vitamin E deficiency were symptomatic and had complete villous atrophy. Thirty-one patients had insufficiency of 25 (OH) D, which was less than the reported frequency of vitamin D insufficiency in the general pediatric population in the United States in 2004. None of the patients were receiving vitamin supplements at the time of diagnosis. CONCLUSIONS: Fat-soluble vitamin deficiencies are uncommon in children with new diagnosis of CD. Routine measuring of fat-soluble vitamins levels may not be necessary.