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Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

Cardiac rehabilitation (CR) has been shown to be safe and effective, but few health conditions qualify individuals for these services. The purpose of this article was to review the evidence surrounding exercise testing and programming for populations not currently referred to CR and less familiar to professionals in these settings.Although cardiac rehabilitation (CR) is safe and highly effective for individuals with various cardiovascular health conditions, to date there are only seven diagnoses or procedures identified by the Centers for Medicare & Medicaid Services that qualify for referral. When considering the growing number of individuals with cardiovascular disease (CVD), or other health conditions that increase the risk for CVD, it is important to determine the extent for which CR could benefit these populations. Furthermore, there are some patients who may currently be eligible for CR (spontaneous coronary artery dissection, left ventricular assistant device) but make up a relatively small proportion of the populations that are regularly attending and participating. Thus, these patient populations and special considerations for exercise might be less familiar to professionals who are supervising their programs. The purpose of this review is to summarize the current literature surrounding exercise testing and programming among four specific patient populations that either do not currently qualify for (chronic and end-stage renal disease, breast cancer survivor) or who are eligible but less commonly seen in CR (sudden coronary artery dissection, left ventricular assist device). While current evidence suggests that individuals with these health conditions can safely participate in and may benefit from supervised exercise programming, there is an immediate need for high-quality, multisite clinical trials to develop more specific exercise recommendations and support the inclusion of these populations in future CR programs.

IMPORTANCE: Spontaneous coronary artery dissection (SCAD), an idiopathic disorder that predominantly affects young to middle-aged women, has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden cardiac death. OBJECTIVE: To identify common single-nucleotide variants (SNVs) associated with SCAD susceptibility. DESIGN, SETTING, AND PARTICIPANTS: This single-center genome-wide association study examined approximately 5 million genotyped and imputed SNVs and subsequent SNV-targeted replication analysis results in individuals enrolled in the Mayo Clinic SCAD registry from August 30, 2011, to August 2, 2018. Data analysis was performed from June 21, 2017, to December 30, 2019. MAIN OUTCOMES AND MEASURES: Genetic loci and positional candidate genes associated with SCAD. RESULTS: This study included 484 white women with SCAD (mean [SD] age, 46.6 [9.2] years) and 1477 white female controls in the discovery cohort (mean [SD] age, 64.0 [14.5] years) and 183 white women with SCAD (mean [SD] age, 47.1 [9.9] years) and 340 white female controls in the replication cohort (mean [SD] age, 51.0 [15.3] years). Associations with SCAD risk reached genome-wide significance at 3 loci (1q21.3 [OR, 1.78; 95% CI, 1.51-2.09; P = 2.63 × 10−12], 6p24.1 [OR, 1.77; 95% CI, 1.51-2.09; P = 7.09 × 10−12], and 12q13.3 [OR, 1.67; 95% CI, 1.42-1.97; P = 3.62 × 10−10]), and 7 loci had evidence suggestive of an association (1q24.2 [OR, 2.10; 95% CI, 1.58-2.79; P = 2.88 × 10−7], 3q22.3 [OR, 1.47; 95% CI, 1.26-1.71; P = 6.65 × 10−7], 4q34.3 [OR, 1.84; 95% CI, 1.44-2.35; P = 9.80 × 10−7], 8q24.3 [OR, 2.57; 95% CI, 1.76-3.75; P = 9.65 × 10−7], 15q21.1 [OR, 1.75; 95% CI, 1.40-2.18; P = 7.23 × 10−7], 16q24.1 [OR, 1.91; 95% CI, 1.49-2.44; P = 2.56 × 10−7], and 21q22.11 [OR, 2.11; 95% CI, 1.59-2.82; P = 3.12 × 10−7]) after adjusting for the top 5 principal components. Associations were validated for 5 of the 10 risk alleles in the replication cohort. In a meta-analysis of the discovery and replication cohorts, associations for the 5 SNVs were significant, with relatively large effect sizes (1q21.3 [OR, 1.77; 95% CI, 1.54-2.03; P = 3.26 × 10−16], 6p24.1 [OR, 1.71; 95% CI, 1.49-1.97; P = 4.59 × 10−14], 12q13.3 [OR, 1.69; 95% CI, 1.47-1.94; P = 1.42 × 10−13], 15q21.1 [OR, 1.79; 95% CI, 1.48-2.17; P = 2.12 × 10−9], and 21q22.11 [OR, 2.18; 95% CI, 1.70-2.81; P = 1.09 × 10−9]). Each index SNV was within or near a gene highly expressed in arterial tissue and previously linked to SCAD (PHACTR1) and/or other vascular disorders (LRP1, LINC00310, and FBN1). CONCLUSIONS AND RELEVANCE: This study revealed 5 replicated risk loci and positional candidate genes for SCAD, most of which are associated with extracoronary arteriopathies. Moreover, the alternate alleles of 3 SNVs have been previously associated with atherosclerotic coronary artery disease, further implicating allelic susceptibility to coronary artery atherosclerosis vs dissection.

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.

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.

The etiology and significance of coronary artery tortuosity (TCA) among patients with spontaneous coronary artery dissection (SCAD) are unknown. The aim of this prospective imaging cohort study was to report echocardiographic findings and evaluate whether TCA correlates with cardiac anatomy and function among patients with SCAD. Comorbidities including fibromuscular dysplasia (FMD) and outcomes were also assessed.

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.

Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome, myocardial infarction, and sudden death, particularly among young women and individuals with few conventional atherosclerotic risk factors. Patient-initiated research has spurred increased awareness of SCAD, and improved diagnostic capabilities and findings from large case series have led to changes in approaches to initial and long-term management and increasing evidence that SCAD not only is more common than previously believed but also must be evaluated and treated differently from atherosclerotic myocardial infarction. High rates of recurrent SCAD; its association with female sex, pregnancy, and physical and emotional stress triggers; and concurrent systemic arteriopathies, particularly fibromuscular dysplasia, highlight the differences in clinical characteristics of SCAD compared with atherosclerotic disease. Recent insights into the causes of, clinical course of, treatment options for, outcomes of, and associated conditions of SCAD and the many persistent knowledge gaps are presented.

Spontaneous coronary artery dissection is a relatively rare cause of myocardial infarction affecting primarily young women. We reported on 9 patients who began cardiac rehabilitation for an average of 12 days after their event, completed 28 sessions, and improved exercise capacity, body composition, and mental health indices.

Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome and sudden death in young persons, particularly women. Associated conditions include fibromuscular dysplasia, peripartum status, and episodes of extreme emotion or exercise. Because of heightened awareness and improved diagnostic accuracy, it is increasingly important for clinicians to understand SCAD. Moreover, short-term and long-term management strategies diverge from typical strategies for atherosclerotic disease. In this Concise Review, we aim to highlight the key points about SCAD, including presentation, diagnosis, associated conditions, and short-term and long-term management.

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Depression and anxiety after myocardial infarction (MI) are common and associated with increased morbidity and mortality. The epidemiology and pathophysiology of MI due to spontaneous coronary artery dissection (SCAD) differs substantially from atherosclerotic MI, and rates of mental health comorbidities after SCAD are unknown. We aimed to determine the prevalence and predictors of depressionanxiety in SCAD survivors.

A 46-year-old woman with no major medical history presented to the emergency department with chest pain and evidence of anterior, anterolateral, and inferior ST-elevation myocardial infarction. Her condition quickly deteriorated into cardiogenic shock with ventricular arrhythmia. Despite revascularization of the left anterior descending artery and intravenous inotrope and antiarrhythmic therapy, her unstable hemodynamics and arrhythmias persisted. Early emergency initiation of venoarterial extracorporeal membrane oxygenation (ECMO) led to prompt hemodynamic and rhythm stability; however, adequate endogenous cardiac output did not ensue, and she was not able to be weaned from ECMO until hospital day 8. She subsequently recovered and continues to do well in the outpatient setting. This case demonstrates the remarkable hemodynamic and rhythm stability that early initiation of ECMO can provide in the setting of unstable myocardial infarction.

Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin. Clinical features and prognosis remain insufficiently characterized.

Pregnancy-associated myocardial infarction is a primary contributor to maternal cardiovascular morbidity and mortality. Specific attention to the cause of myocardial infarction, diagnostic evaluation, treatment strategies, and postevent care is necessary when treating women with pregnancy-associated myocardial infarction. This review summarizes the current knowledge, consensus statements, and essential nuances.

Introduction:Spontaneous coronary artery dissection (SCAD) presents as an acute coronary syndrome, often in women of childbearing age. The characteristics and outcomes of pregnancies in women with prior SCAD are incompletely understood.Objective:To describe risk of future events among women who became pregnant after SCAD.Methods:Among 1003 women with history of SCAD enrolled in the Mayo Clinic SCAD Registry from 8/30/2011-12/31/2018, 22 women had pregnancy after the initial SCAD (31 post-SCAD pregnancies). All women in the registry without recent clinical assessment were contacted to update individual cardiovascular and obstetric data.Results:Median time to conception following initial SCAD was 18 (3-39) months with a median age of 37 (28-42) years (Table). Nineteen (61%) pregnancies resulted in live births: 12 term vaginal deliveries, 6 term cesarean sections, and 1 emergent preterm cesarean section. Of the 14 (74%) women who breastfed, one ceased because of chest pain and another due to recurrent SCAD. At median follow-up of 4.6 years after the most recent pregnancy, recurrent SCAD occurred in only 2 women (9%) with a 5.3% 5-year Kaplan-Meier estimated rate of recurrence. One recurrence was at 9 weeks postpartum (her first SCAD was not postpartum), and the other had two recurrences >10 years after delivery (her first SCAD was postpartum).Conclusions:The majority of women with history of SCAD and subsequent pregnancy were older mothers who did not experience SCAD during or after pregnancy, suggesting a multifactorial precipitating etiology to recurrent SCAD beyond pregnancy alone. Despite these somewhat reassuring findings, given the potential cardiovascular consequences of a recurrent event we do not believe they constitute sufficient evidence to revise current recommendations to avoid pregnancy after SCAD.

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