The genetics of spontaneous coronary artery dissection: a scoping review.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a multifactorial process that involves predisposing factors and precipitating stressors. Genetic abnormality has been implicated to play a mechanistic role in the development of SCAD. This systematic review aims to summarize the current evidence concerning the link between SCAD and genetic abnormalities. METHODS: We reviewed original studies published until May 2023 that reported SCAD patients with a genetic mutation by searching PubMed, Embase Ovid, and Google Scholar. Registries, cohort studies, and case reports were included if a definitive SCAD diagnosis was reported, and the genetic analysis was performed. Exclusion criteria included editorials, reviews, letters or commentaries, animal studies, meeting papers, and studies from which we were unable to extract data. Data were extracted from published reports. RESULTS: A total of 595 studies were screened and 55 studies were identified. Among 116 SCAD patients with genetic abnormalities, 20% had mutations in the COL gene, 13.70% TLN1 gene, and 8.42% TSR1 gene. Mutations affecting the genes encoding COL and TLN1 were most frequently reported (20 and 13.7%, respectively). Interestingly, 15 genes of this collection were also reported in patients with thoracic aortic diseases as well. The genetic commonality between fibromuscular dysplasia (FMD) and SCAD was also included. CONCLUSION: In this review, the inherited conditions and reported genes of undetermined significance from case reports associated with SCAD are collected. A brief description of the encoded protein and the clinical features associated with pathologic genes is provided. Current data suggested that the diagnostic yield of genetic studies for patients with SCAD would be low and routine genetic screening of such patients with no clinical features indicative of associated disorders remains debatable. This review can be used as a guide for clinicians to recognize inherited syndromic and nonsyndromic disorders associated with SCAD.

Clinical Presentation and Therapy of Coronary Artery Anomalies.

There are two major coronary arteries that arise normally directly above the aortic valve in the sinus. The left main coronary artery (LCA or LMCA) arises from the left coronary sinus and divides shortly after its origin into the left anterior descending and the circumflex coronary arteries (LCX). Branches of the left anterior descending (LAD) coronary artery include the left conus, septal, and diagonal arteries. Branches of the circumflex coronary artery may include the sinus node artery, Kugel's artery, marginal arteries, and the left atrial circumflex artery (Fig. 47.1). The LAD follows the interventricular septum to the apex, the LCX turns posterior, follows the atrioventricular groove between the left atrium and ventricle to the coronary sinus. Branches of the right coronary artery (RCX) include the conal branch, the sinus node artery, an atrial branch, the right ventricular muscle branches (including the acute marginal branch), the posterior descending coronary artery, the atrioventricular node artery, and septal branches (Fig. 47.2). The RCX follows the atrioventricular groove between the right atrium and ventricle. The "dominant coronary artery" is the one giving rise to the posterior descending coronary artery. It originates from the right coronary artery in 80% of people.

Myocardial Infarction in Young Adults: Diagnosis Begins Through Inspection.

Spontaneous coronary artery dissection (SCAD) is an atypical cause of myocardial infarction, predominantly seen in women. Among various predisposing factors, genetic vasculopathies such as connective tissue diseases significantly contribute to SCAD. This report discusses a 36-year-old male diagnosed with vascular type Ehlers-Danlos syndrome following an anterior myocardial infarction and explores relevant literature.

Aberrant left coronary artery from the pulmonary artery with patent ductus arteriosus - a case report and review of the literature.

BACKGROUND: Aberrant left coronary artery from pulmonary artery (ALCAPA) is a very rare congenital heart defect. Its coexistence with patent ductus arteriosus (PDA) is extremely rare. The high pressures created by the left-to-right shunt in the pulmonary arteries can delay symptoms and create a real challenge in diagnosing ALCAPA. Missing this diagnosis can have severe results, including extensive ischemia and sudden death. CASE PRESENTATION: We present a case of an infant born with a large PDA. Initially treated conservatively, however, due to congestive heart failure and lack of weight gain, she underwent surgical ligation of the PDA at the age of four and a half months. Following surgery, she developed pulmonary edema. Echocardiography revealed decreased ventricular function. ECG revealed ST elevations on lateral leads, and serum troponin was significantly increased. The patient underwent cardiac magnetic resonance imaging (MRI), which revealed signs of wall ischemia and decreased function of the left ventricle (LV) with unclear coronary anatomy. Diagnostic catheterization revealed an ALCAPA. She underwent surgical intervention, and the left coronary artery was re-implanted in the aortic sinus. Follow-up revealed slow improvement of cardiac function. DISCUSSION AND LITERATURE REVIEW: The coexistence of PDA and ALCAPA is a very rare occurrence. We found at least 10 reported cases in the literature. Delayed diagnosis might be detrimental. The prognosis of these patients is variable. CONCLUSION: An unusual post-surgical course following PDA repair requires a high index of suspicion and appropriate evaluation for ALCAPA, preferably with angiography.

Migraine headache in patients with spontaneous coronary artery dissection: A report of the iSCAD Registry.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified. METHODS: Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine. RESULTS: Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, p = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, p = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [p = 0.0004] and 35.3% vs 26.7% [p = 0.0099], respectively). CONCLUSIONS: Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities.

The Genetics of Human Congenital Coronary Vascular Anomalies.

The genetics of human congenital coronary vascular anomalies (hCCVA) remains largely underresearched. This is surprising, because although coronary vascular defects represent a relatively small proportion of human congenital heart disease (CHD), hCCVAs are clinically significant conditions. Indeed, hCCVA frequently associate to other congenital cardiac structural defects and may even result in sudden cardiac death in the adult. In this brief chapter, we will attempt to summarize our current knowledge on the topic, also proposing a rationale for the development of novel approaches to the genetics of hCCVA.

Congenital Coronary Blood Vessel Anomalies: Animal Models and the Integration of Developmental Mechanisms.

Coronary blood vessels are in charge of sustaining cardiac homeostasis. It is thus logical that coronary congenital anomalies (CCA) directly or indirectly associate with multiple cardiac conditions, including sudden death. The coronary vascular system is a sophisticated, highly patterned anatomical entity, and therefore a wide range of congenital malformations of the coronary vasculature have been described. Despite the clinical interest of CCA, very few attempts have been made to relate specific embryonic developmental mechanisms to the congenital anomalies of these blood vessels. This is so because developmental data on the morphogenesis of the coronary vascular system derive from complex studies carried out in animals (mostly transgenic mice), and are not often accessible to the clinician, who, in turn, possesses essential information on the significance of CCA. During the last decade, advances in our understanding of normal embryonic development of coronary blood vessels have provided insight into the cellular and molecular mechanisms underlying coronary arteries anomalies. These findings are the base for our attempt to offer plausible embryological explanations to a variety of CCA as based on the analysis of multiple animal models for the study of cardiac embryogenesis, and present them in an organized manner, offering to the reader developmental mechanistic explanations for the pathogenesis of these anomalies.

Spontaneous coronary artery dissection (SCAD): A contemporary review.

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction that most frequently affects younger women, making it an important cause of morbidity and mortality within these demographics. The evolution of intracoronary imaging, improved diagnosis with coronary angiography, and ongoing research efforts and attention via social media, has led to increasing recognition of this previously underdiagnosed condition. In this review, we provide a summary of the current body of knowledge, as well as focused updates on the pathogenesis of SCAD, insights on genetic susceptibility, contemporary diagnostic tools, and immediate, short- and long-term management.

Implantable Cardioverter-Defibrillator Placement in Spontaneous Coronary Artery Dissection: A Case Report.

BACKGROUND Spontaneous coronary artery dissection can present with acute coronary syndrome, ventricular arrhythmias, or sudden cardiac death. Implantable cardioverter-defibrillator placement in patients with spontaneous coronary artery dissection is controversial. The purpose of publishing this case is to inform physicians of potential benefits of implantable cardioverter-defibrillator implantation in patients with spontaneous coronary artery dissection. CASE REPORT A 55-year-old woman presented with chest pain, with an electrocardiogram revealing anterior ST-elevation myocardial infarction and troponin peak of 53.8 ng/mL. Coronary angiography revealed mid-left anterior descending artery occlusion, with appearance of spontaneous coronary artery dissection that was not amenable to revascularization. The decision was made to treat medically. In recovery, the patient experienced ventricular fibrillation arrest. The patient was defibrillated once with achievement of return of spontaneous circulation. An Impella CP was placed to stabilize the patient. After the patient was stabilized, an implantable cardioverter-defibrillator was placed. CONCLUSIONS Data on potential benefits of implantable cardioverter-defibrillator placement in patients with spontaneous coronary artery dissection are limited. Most patients with spontaneous coronary artery dissection recover normal coronary architecture; however, there are no guidelines for implantable cardioverter-defibrillator placement in patients with spontaneous coronary artery dissection. Patients with spontaneous coronary artery dissection with high-risk features may benefit from implantable cardioverter-defibrillator for secondary prevention of ventricular arrhythmia and sudden cardiac death, as shown with this case.

From Atherosclerosis to Spontaneous Coronary Artery Dissection: Defining a Clinical and Genetic Risk Spectrum for Myocardial Infarction.

PURPOSE OF REVIEW: Spontaneous coronary artery dissection (SCAD) has been increasingly recognized as a significant cause of acute myocardial infarction (AMI) in young and middle-aged women and arises through mechanisms independent of atherosclerosis. SCAD has a multifactorial etiology that includes environmental, individual, and genetic factors distinct from those typically associated with coronary artery disease. Here, we summarize the current understanding of the genetic factors contributing to the development of SCAD and highlight those factors which differentiate SCAD from atherosclerotic coronary artery disease. RECENT FINDINGS: Recent studies have revealed several associated variants with varying effect sizes for SCAD, giving rise to a complex genetic architecture. Associated genes highlight an important role for arterial cells and their extracellular matrix in the pathogenesis of SCAD, as well as notable genetic overlap between SCAD and other systemic arteriopathies such as fibromuscular dysplasia and vascular connective tissue diseases. Further investigation of individual variants (including in the associated gene PHACTR1) along with polygenic score analysis have demonstrated an inverse genetic relationship between SCAD and atherosclerosis as distinct causes of AMI. SCAD represents an increasingly recognized cause of AMI with opposing clinical and genetic risk factors from that of AMI due to atherosclerosis, and it is often associated with complex underlying genetic conditions. Genetic study of SCAD on a larger scale and with more diverse cohorts will not only further our evolving understanding of a newly defined genetic spectrum for AMI, but it will also inform the clinical utility of integrating genetic testing in AMI prevention and management moving forward.

Anomalous circumflex artery encircling the aortic annulus: implications for mitral valve repair.

Injury to coronary arteries during mitral surgery is a rare but life-threatening procedural complication, an anomalous origin and course of the left circumflex artery (LCx) increase this risk. Recognizing the anomaly by the characteristic angiographic pattern and identifying its relationship with the surrounding anatomical structure using imaging techniques, mainly transesophageal echocardiography (TOE) or coronary computed tomography angiography (CCTA), is of crucial importance in setting up the best surgical strategy. We report a case of anomalous origin of a circumflex artery (LCx) from the proximal portion of the right coronary artery (RCA) with a pathway running retroaortically through the mitro-aortic space. An integrated diagnostic approach using a multidisciplinary team with a cardiologist and an imaging radiologist allowed us to decide the surgical strategy. We successfully performed a mitral valvular repair using a minimally invasive minithoracotomic approach and implanting a complete semirigid ring.

Minimally invasive left axillary thoracotomy for the total repair of fallot, dextrocardia, situs inversus and anomalous coronary artery origins.

We present a rare case of tetralogy of Fallot accompanied with dextrocardia, situs inversus and anomalous origin of the right coronary artery. Total repair was accomplished successfully using a minimally invasive left axillary thoracotomy.

NASCI case of the month: "Unroofed coronary sinus without persistent left-sided superior vena cava".

Unroofed sinus is categorized into four subtypes. Types I and II represent complete unroofing with or without an LSVC, respectively [1]. Types III and IV are partial unroofing involving the mid-CS (type III) or near the LA appendage and left superior pulmonary vein (type IV) [1]. CT has advantages over echocardiography in detection of this anomaly (illustrated in this case) as well as in precise delineation of defect and associated findings (presence or absence of LSVC). Short axis reconstructions at the level of CS are helpful in diagnosis. Considerations for repair include location of CS defect, presence of LSVC and other abnormalities as well as comorbidity risks [2].

Spontaneous Coronary Artery Dissection in a Male Patient With Fibromuscular Dysplasia.

A male patient presented with cardiac arrest attributed to anterior ST-segment elevation myocardial infarction from type 1 spontaneous coronary artery dissection. Subsequent imaging confirmed fibromuscular dysplasia in noncoronary arterial segments. The patient was started on guideline-directed medical therapy and referred to cardiac rehabilitation, showing substantial improvements in clinical status. With greater awareness and advancements in imaging, spontaneous coronary artery dissection has been more frequently recognized, and although as many as 81% to 92% of all cases occur in female patients, it can be seen among men, as well. Adjunctive imaging for arteriopathies may help establish the diagnosis for equivocal causes of acute coronary syndrome in women and men.

Spontaneous coronary artery dissection in patients with prior psychophysical stress: a systematic review of case reports and case series.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed cause of acute coronary syndrome, particularly in younger women. Due to limited information about SCAD, case reports and case series can provide valuable insights into its features and management. This study aimed to comprehensively evaluate the features of SCAD patients who experienced psychophysical stress before the SCAD event. METHODS: We conducted an electronic search of PubMed, Scopus, and Web of Science from inception until January 7, 2023. We included case reports or series that described patients with SCAD who had experienced psychophysical stress before SCAD. Patients with pregnancy-associated SCAD were excluded from our analysis. RESULTS: In total, we included 93 case reports or series describing 105 patients with SCAD. The average patient age was 44.29 ± 13.05 years and a total of 44 (41.9%) of patients were male. Among the included SCAD patients the most prevalent comorbidities were fibromuscular dysplasia (FMD) and hypertension with the prevalence of 36.4 and 21.9%, respectively. Preceding physical stress was more frequently reported in men than in women; 38 out of 44 (86.4%) men reported physical stress, while 36 out of 61 (59.1%) females reported physical stress (p value = 0.009). On the other hand, the opposite was true for emotional stress (men: 6 (13.6%)), women: 29 (47.6%), p value < 0.001). Coronary angiography was the main diagnostic tool. The most frequently involved artery was the left anterior descending (LAD) (62.9%). In our study, recurrence of SCAD due to either the progression of a previous lesion or new SCAD in another coronary location occurred more frequently in those treated conservatively, however the observed difference was not statistically significant (p value = 0.138). CONCLUSION: While physical stress seems to precede SCAD in most cases, emotional stress is implicated in females more than males.

Arterial switch operation in a child with commissural malalignment and unusual coronary anatomy.

The arterial switch operation has evolved to become the treatment of choice for transposition of the great arteries and is one of the greatest success stories in congenital heart surgery. The most crucial step of the operation is the coronary artery translocation; therefore, it is of paramount importance for surgeons to know every single detail about the morphology and spatial relationships of the coronary arteries and the roots of the great vessels. However, sometimes the surgeon may face unfavourable scenarios such as major commissural malalignment and anomalous coronary artery patterns and need to be prepared to carry out a successful coronary artery translocation. Herein, we demonstrate that the trapdoor technique is useful for transferring coronary arteries in a neonate with major commissural malalignment and unusual coronary anatomy during the arterial switch operation.