Tweet, Marysia S.

Background: Spontaneous coronary artery dissection (SCAD) is an uncommon idiopathic disorder predominantly affecting young, otherwise healthy women. Rare familial cases reveal a genetic predisposition to disease. The aim of this study was to identify a novel susceptibility gene for SCAD. Methods: Whole-exome sequencing was performed in a family comprised of 3 affected individuals and filtered to identify rare, predicted deleterious, segregating variants. Immunohistochemical staining was used to evaluate protein expression of the identified candidate gene. The prevalence and spectrum of rare (<0.1%) variants within binding domains was determined by next-generation sequencing or denaturing high-performance liquid chromatography in a sporadic SCAD cohort of 675 unrelated individuals. Results: We identified a rare heterozygous missense variant within a highly conserved β-integrin–binding domain of TLN1 segregating with familial SCAD. TLN1 encodes talin 1—a large cytoplasmic protein of the integrin adhesion complex that links the actin cytoskeleton and extracellular matrix. Consistent with high mRNA expression in arterial tissues, robust immunohistochemical staining of talin 1 was demonstrated in coronary arteries. Nine additional rare heterozygous missense variants in TLN1 were identified in 10 sporadic cases. Incomplete penetrance, suggesting genetic or environmental modifiers of this episodic disorder, was evident in the familial case and 5 individuals with sporadic SCAD from whom parental DNA was available. Conclusions: Our findings reveal TLN1 as a disease-associated gene in familial and sporadic SCAD and, together with abnormal vascular phenotypes reported in animal models of talin 1 disruption, implicate impaired structural integrity of the coronary artery cytoskeleton in SCAD susceptibility.

Background Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome predominantly in women without usual cardiovascular risk factors. Many have a history of migraine headaches, but this association is poorly understood. This study aimed to determine migraine prevalence among SCAD patients and assess differences in clinical factors based on migraine history. Methods and Results A cohort study was conducted using the Mayo Clinic SCAD “Virtual” Multi‐Center Registry composed of patients with SCAD as confirmed on coronary angiography. Participant‐provided data and records were reviewed for migraine history, risk factors, SCAD details, therapies, and outcomes. Among 585 patients (96% women), 236 had migraine history; the lifetime and 1‐year prevalence of migraine were 40% and 26%, respectively. Migraine was more common in SCAD women than comparable literature‐reported female populations (42% versus 24%, P <0.0001; 42% versus 33%, P <0.0001). Among all SCAD patients, those with migraine history were more likely to be female (99.6% versus 94%; P =0.0002); have SCAD at a younger age (45.2±9.0 years versus 47.6±9.9 years; P =0.0027); have depression (27% versus 17%; P =0.025); have recurrent post‐SCAD chest pain at 1 month (50% versus 39%; P =0.035); and, among those assessed, have aneurysms, pseudoaneurysms, or dissections (28% versus 18%; P =0.018). There was no difference in recurrent SCAD at 5 years for those with versus without migraine (15% versus 19%; P =0.39). Conclusions Many SCAD patients have a history of migraine. SCAD patients with migraine are younger at the time of SCAD; have more aneurysms, pseudoaneurysms, and dissections among those imaged; and more often report a history of depression and post‐SCAD chest pain. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01429727, NCT01427179.

Background: Risks and mechanisms of extension of conservatively managed spontaneous coronary artery dissection (SCAD) remain incompletely understood. Study objectives were to (1) evaluate mechanisms of early SCAD evolution through serial angiographic analysis, and (2) determine predictors of early SCAD progression. Methods and Results: Retrospective registry study of patients with SCAD managed with an initial conservative strategy (n=240). Patients who experienced significant SCAD progression within 14 days, defined as clinical worsening plus new critical coronary obstruction on repeat angiography, were compared with remaining controls. A total of 42 of 240 (17.5%) experienced significant SCAD progression after index conservative approach; 91% by day 6. Isolated intramural hematoma (IMH) at baseline (no intimal dissection) was observed more frequently in those experiencing progression compared with controls (69.1% versus 44.4%; P =0.004). Multivariable predictors of SCAD progression included lesion severity, multivessel involvement, and isolated IMH. To investigate mechanisms of SCAD evolution, all repeat angiograms ≤14 days were compared with corresponding baselines (n=82 patient angiogram pairs). Of those with isolated IMH at baseline, 20% developed intimal dissection at repeat study. IMH was associated with greater longitudinal lesion extension (11.5 versus 2.8 mm; P =0.01), worsening Thrombolysis in Myocardial Infarction flow (−0.8 versus 0.1; P =0.003), and a nonsignificant lower rate of angiographic improvement (20.0% versus 31.3%; P =0.16) compared with the group with baseline intimal dissection. Optical coherence tomography subgroup analysis (n=17) indicated intimo-medial thickness to be lowest at the midpoint of IMH. Conclusions: Conservatively managed SCAD carries a 1:6 hazard for serious deterioration within 6 days. The risk was higher in those with isolated IMH at baseline. IMH often precedes development of intimal dissection, which has implications for mechanisms of SCAD.

Objectives: To investigate the role of endothelial function in patients with previous spontaneous coronary artery dissection. Background: Mechanisms underlying spontaneous coronary artery dissection, including a possible contribution from endothelial dysfunction, remain poorly understood. Methods: This was a single center, retrospective study of patients with a prior spontaneous coronary artery dissection episode who underwent invasive endothelial function testing in the cardiac catheterization laboratory for evaluation of recurrent chest pain. Coronary epicardial and microvascular responses to acetylcholine, adenosine, and nitroglycerine were assessed. Findings were compared to a reference group of normal controls ( n=232). Results: A total of 10 patients with prior angiographically confirmed spontaneous coronary artery dissection were referred for coronary endothelial function testing. The median coronary flow reserve was 2.8 (interquartile range (IQR) 2.3, 3.6). The median change in coronary diameter with acetylcholine was −0.9% (IQR −23.9, 4.2). The median increase in peak coronary blood flow following acetylcholine administration was 91.4% (IQR 9.1, 105.7), which was similar to the response observed in a reference group of patients (median age 51 years, 96% women) from our laboratory with normal microvascular responses to acetylcholine: 107.4% (IQR 75.5, 165.7; P=0.20). Four patients (40%) had an abnormal microvascular response to acetylcholine, with less than a 50% increase in coronary blood flow, and all but one patient had left anterior descending artery or multivessel spontaneous coronary artery dissection. Conclusion: Coronary epicardial and microvascular vasomotor dysfunction is not a predominant feature of spontaneous coronary artery dissection. Endothelial dysfunction is not implicated as the principal underlying mechanism.

Spontaneous coronary artery dissection is a nonatherosclerotic etiology of acute coronary syndrome, including sudden cardiac death, which frequently affects younger women. This review highlights contemporary knowledge regarding spontaneous coronary artery dissection demographics, prevalence, diagnosis, presentation, and associated conditions and risks, inpatient treatment, major adverse clinical events, and outpatient management decisions.

Background: The coronary computed tomography angiography features of acute spontaneous coronary artery dissection, an important cause of acute coronary syndrome in young women, have not been assessed. Methods: The “Virtual” Multicenter Mayo Clinic Spontaneous Coronary Artery Dissection Registry was established in 2010 and includes retrospective and prospective patient data. Retrospective assessment of acute coronary computed tomography angiography images was performed for 14 patients (16 vessels) who had images performed within two days of invasive coronary angiography diagnosis of acute spontaneous coronary artery dissection. Results: Four pertinent diagnostic coronary features of acute spontaneous coronary artery dissection were observed in order of prevalence: 1) abrupt luminal stenosis (64%); 2) intramural hematoma (50%); 3) tapered luminal stenosis (36%); and 4) dissection (14%). Additional findings include epicardial fat stranding (42%), coronary tortuosity (29%), and coronary bridge (14%). Fifty percent of patients had myocardial hypoperfusion in the myocardial distribution of the dissected coronary artery. Conclusions: We define key coronary computed tomography angiography features of acute spontaneous coronary artery dissection, the most common of which are abrupt luminal stenosis and intramural hematoma. Importantly, intramural hematoma appears similar to noncalcified atherosclerotic plaque, emphasizing the importance of invasive coronary angiography for acute diagnosis of spontaneous coronary artery dissection until the sensitivity and specificity of coronary computed tomography angiography is better understood.

Background: There is limited understanding of the role of cardiac computed tomography angiography (CCTA) for assessment of patients with spontaneous coronary artery dissection (SCAD). Methods: In this report we describe the diagnostic utility of CCTA in three young women presenting with signs and symptoms of myocardial ischemia who were eventually diagnosed with SCAD. Results: None of the women had traditional atherosclerotic risk factors. SCAD was not initially identified on CCTA in any of the three women, but was visualized during retrospective analysis in two patients after invasive coronary angiography. In two patients follow-up CCTA imaging was used successfully for subsequent management. Conclusions: In patients presenting with signs or symptoms of acute coronary syndrome, SCAD may be missed or not detectable on CCTA. A negative CCTA should not exclude a diagnosis of SCAD, and invasive coronary angiography should be considered for further evaluation.

Abstract Ten case reports of disseminated Mycobacterium chimaera infections associated with cardiovascular surgery were published from Europe. We report 3 cases of disseminated M chimaera infections with histories of aortic graft and/or valvular surgery within the United States. Two of 3 patients demonstrated ocular involvement, a potentially important clinical finding.