Young Hearts at Risk: Exploring the Complexities of SCAD in Women Aged 19-30 By Mary Pershall Susan Webb A thesis submitted to the School of Radiologic Sciences in collaboration with a research agenda team In partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN RADIOLOGIC SCIENCES (MSRS) WEBER STATE UNIVERSITY Ogden, Utah December 15, 2023 ii THE WEBER STATE UNIVERSITY GRADUATE SCHOOL SUPERVISORY COMMITTEE APPROVAL of a thesis submitted by Mary Pershall Susan Webb This thesis has been read by each member of the following supervisory committee and by majority vote found to be satisfactory. ______________________________ Dr. Tanya Nolan, EdD Chair, School of Radiologic Sciences ______________________________ Chris Steelman, MS Director of MSRS Cardiac Specialist ______________________________ Dr. Laurie Coburn, EdD Director of MSRS RA ______________________________ Dr. Robert Walker, PhD Director of MSRS iii THE WEBER STATE UNIVERSITY GRADUATE SCHOOL RESEARCH AGENDA STUDENT APPROVAL of a thesis submitted by Mary Pershall Susan Webb This thesis has been read by each member of the student research agenda committee and by majority vote found to be satisfactory. Date Jan 9, 2024 ______________________ Jan 8, 2024 ______________________ Mary Pershall ____________________________________ Mary Pershall Mary Pershall (Jan 9, 2024 10:54 MST) Susan Webb Susan Webb (Jan 8, 2024 15:30 PST) ____________________________________ Susan Webb iv Abstract Spontaneous Coronary Artery Dissection (SCAD) is an uncommon yet increasingly recognized cause of ACS, particularly in young women. Despite progress in recognition, misdiagnosis remains a significant risk, given the relatively young age and absence of conventional atherosclerotic risk factors in SCAD patients. Early and accurate diagnosis is paramount due to substantial differences in management compared to atherosclerotic ACS. However, significant gaps persist in establishing high-quality, evidence-based guidelines for optimal SCAD treatment. This qualitative analysis investigates 23 unique reports of SCAD in young women aged 19-30. Using a case study design, we explore the common contributing factors, diagnostic challenges, trends in management strategies, and outcomes in this population. With our findings, we aim to increase awareness, address existing knowledge gaps, and promote a more informed approach to managing SCAD in young women. Of analyzed case reports, pregnancy-related SCAD (P-SCAD) was the most prevalent contributing factor, occurring in 12 patients. Young age, lack of traditional risk factors, and clinical presentations resembling other cardiac conditions were identified as the main diagnostic challenges. Medical management and revascularization were almost equally as common and were guided by hemodynamic stability, clinical presentation, and vessel distribution. Short-term and long-term outcomes varied widely, with factors such as delayed treatment, treatment type, and SCAD severity influencing results. Complications included cardiogenic shock, dissection extension, recurrent myocardial infarction, and reduced left ventricular function. v These findings highlight the prevalence of AMI in young women, emphasizing the severity of postpartum SCAD (P-SCAD) and the necessity for tailored diagnostic and treatment approaches in this population. Enhanced awareness and specialized management strategies for SCAD in young women are imperative to are imperative to ensure timely and accurate diagnosis, improve treatment outcomes, and improve patient outcomes. vi Table of Contents Chapter 1: Introduction ....................................................................................................9 Background .............................................................................................................10 Statement of the Problem .........................................................................................12 Research Questions ..................................................................................................13 Nature of the Study ..................................................................................................13 Research Method and Design......................................................................................................... 13 Qualitative Research ..................................................................................................................... 14 Case Study Design ......................................................................................................................... 14 Variables and Constructs ............................................................................................................... 14 Data Collection and Analysis ......................................................................................................... 14 Foundational Support .................................................................................................................... 15 Significance of the Study .........................................................................................15 Definition of Key Terms ..........................................................................................16 Summary .................................................................................................................16 Chapter 2: Clinical Background .....................................................................................18 Introduction .............................................................................................................18 Etiology ...................................................................................................................18 Epidemiology ..........................................................................................................20 Pathophysiology ......................................................................................................21 Evaluation ...............................................................................................................22 Coronary Angiography .................................................................................................................. 23 Intravascular Imaging ................................................................................................................... 24 Coronary Computed Tomography Angiography ............................................................................. 25 Treatment / Management Options ............................................................................25 Conservative Management ............................................................................................................. 25 Revascularization .......................................................................................................................... 26 Medical Management .................................................................................................................... 28 Complications ..........................................................................................................29 Summary .................................................................................................................30 Chapter 3: Literature Reviews .......................................................................................32 Documentation ........................................................................................................32 General Literature Review .......................................................................................32 Prevalence ...............................................................................................................32 Patient Characteristics ..............................................................................................34 Predisposing Factors ................................................................................................36 Pregnancy-Related SCAD .............................................................................................................. 36 Exogenous Hormones .................................................................................................................... 39 Fibromuscular Dysplasia............................................................................................................... 40 Neurological Factors ..................................................................................................................... 42 Rheumatological and Systemic Inflammatory Diseases ................................................................... 43 Genetic Factors ............................................................................................................................. 45 Mental Health................................................................................................................................ 48 Precipitating Factors ................................................................................................50 Emotional and Physical Triggers ................................................................................................... 50 Recreational Drugs........................................................................................................................ 53 vii Clinical Presentation ................................................................................................54 Diagnosis .................................................................................................................60 Early Diagnostic Methods.............................................................................................................. 60 Coronary Angiography and SCAD Lesion Classifications............................................................... 62 Important Considerations .............................................................................................................. 66 Other Angiographic Findings......................................................................................................... 68 Advanced Imaging Techniques ....................................................................................................... 69 Non-Invasive Imaging .................................................................................................................... 72 Treatment / Management Options ............................................................................76 Conservative/Medical Management ............................................................................................... 77 Revascularization .......................................................................................................................... 82 Special Considerations .................................................................................................................. 87 Outcomes.................................................................................................................88 Recurrent SCAD ............................................................................................................................ 89 Treatment Related Outcomes ......................................................................................................... 90 Patient-Related Outcomes.............................................................................................................. 95 Psychological and Quality of Life Outcomes .................................................................................. 98 Summary ............................................................................................................... 100 Case Study Literature Review ................................................................................ 101 Demographics and Patient Characteristics .............................................................. 102 Cardiovascular Risk Factors........................................................................................................ 102 Pregnancy-Related SCAD and Oral Contraceptives ..................................................................... 103 Predisposing and Precipitating Factors ....................................................................................... 104 Coronary Distribution ................................................................................................................. 106 Clinical Presentation .............................................................................................. 107 Acute Coronary Syndrome ........................................................................................................... 107 Severe Presentations.................................................................................................................... 109 Pregnancy-Related SCAD ............................................................................................................ 110 Diagnosis ............................................................................................................... 117 Treatment / Management Strategies ....................................................................... 128 Conservative Medical Therapy..................................................................................................... 128 Percutaneous Coronary Intervention............................................................................................ 130 Coronary Artery Bypass Grafting................................................................................................. 133 Outcomes............................................................................................................... 135 In-Hospital/Short-Term Outcomes ............................................................................................... 135 Intermediate/Long-Term Outcomes .............................................................................................. 138 Delays in Diagnosis and Management ......................................................................................... 140 Counseling and Follow-up ..................................................................................... 142 Summary ............................................................................................................... 144 Chapter 4: Research Method ........................................................................................ 146 Research Questions ................................................................................................ 147 Research Methods and Design(s) ........................................................................... 147 Population ............................................................................................................. 148 Sample ................................................................................................................... 148 Data Collection, Processing, and Analysis ............................................................. 149 Assumptions .......................................................................................................... 149 Limitations ............................................................................................................ 150 Delimitations ......................................................................................................... 151 Ethical Assurances ................................................................................................. 152 viii Summary ............................................................................................................... 153 Chapter 5: Findings ..................................................................................................... 155 Results ................................................................................................................... 155 Evaluation of Findings ........................................................................................... 158 Summary ............................................................................................................... 160 Chapter 6: Implications, Recommendations, and Conclusions ...................................... 161 Recommendations.................................................................................................. 167 Conclusions ........................................................................................................... 169 References ................................................................................................................... 171 9 Chapter 1: Introduction Spontaneous coronary artery dissection (SCAD) represents a significant cause of acute myocardial infarction (AMI) and sudden cardiac death in young to middle-aged women.1–3 It is characterized by a separation of the coronary artery wall, formation of an intramural hematoma (IMH), and obstruction of coronary flow, resulting in myocardial ischemia or infarction.1,2,4,5 Importantly, SCAD is non-iatrogenic and occurs independently from trauma or atherosclerosis.1,2,4,5 The underlying cause of SCAD remains unclear, but likely involves a complex interplay of genetic, hormonal, vascular, and environmental factors.1,3 The diverse clinical presentations of SCAD often resemble those of other cardiac conditions, leading to frequent misdiagnoses and diagnostic delays.6,7 However, Given that treatment strategies for SCAD and atherosclerotic ACS differ broadly, timely and accurate diagnosis becomes vital.8 Due to the limited body of evidence available to guide clinical decision making, current recommendations rely heavily on insights derived from patient series and expert opinions.9 Common treatment methods include medical therapy, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG).6,7,10–12 The choice of treatment should be based on several clinical factors, including presentation, hemodynamic stability, and severity of the dissection.6,7,10–12 Modern series report acute in-hospital mortality of less than 5%, and rates of inhospital recurrent MI, repeat revascularization, or other Major Adverse Cardiovascular Events (MACEs) between 5% to 10%.13 Nevertheless, post-hospital discharge, a substantial percentage of patients may experience recurrent chest pains and MACEs, primarily driven by recurrent SCAD.13 Additionally, female, and postpartum patients 10 often have a worse prognosis, with larger infarcts, lower mean left ventricular ejection fractions, and a higher prevalence of proximal artery dissections.4,13 Cardiovascular disease, particularly AMI, has become an increasingly prevalent concern among young women, even those who do not exhibit traditional atherosclerotic risk factors.14 This shift in disease demographics emphasizes the urgent need for comprehensive strategies to understand, diagnose, and effectively manage conditions such as SCAD within this specific population.14 As the incidence of cardiovascular events rises in young women, it is crucial to increase awareness, research initiatives, and tailored interventions to address the unique challenges posed by these evolving epidemiological trends.14 Background SCAD was once thought to be a rare and potentially life-threatening cause of Acute Coronary Syndrome (ACS), Myocardial Infarction (MI), and sudden cardiac death in peripartum women.15 However, modern imaging techniques, greater awareness among medical professionals, and patient advocacy have revealed a higher prevalence of SCAD, especially among young women.5 SCAD is estimated to account for up to 35% of ACS cases in women under 50 years old, and is recognized as the leading cause of pregnancyrelated MI.2–5 Despite the increased awareness and recognition in recent years, SCAD is still frequently misdiagnosed due to the comparatively low suspicion of ACS in young women, regardless of the clinical presentation.5 This is further compounded by the inherent limitations of angiography and lack of familiarity among clinicians.5 Additionally. There is a concerning trend of women being more susceptible to 11 underdiagnoses, misdiagnoses, or inadequate treatments than their male counterparts.16 This discrepancy can be attributed to the unique clinical presentation of SCAD, its distinct pathophysiology, and the historical underrepresentation of women in medical research.16 The imperative for research in young women with Spontaneous Coronary Artery Dissection (SCAD) is underscored by the complexity of its diagnosis and the distinctive challenges it presents, particularly during pregnancy and postpartum. It is important to recognize that SCAD is distinct from atherosclerotic coronary diseases and has its own set of unique risk factors and associated conditions.5 It is frequently seen in younger women compared to atherosclerotic ACS, with risk factors including pregnancy, postpartum, and fibromuscular dysplasia (FMD).1 The predominant occurrence of SCAD in young females suggests potential links to female sex hormones and environmental stressors, and further supports the reported association with FMD.1 In addition, female and peripartum patients have a significantly higher risk of in-hospital mortality and Major Adverse Cardiovascular Events (MACE). Studies have shown that female SCAD patients, particularly those in the postpartum period, face more challenging circumstances, with a higher probability of severe myocardial damage and dissections in proximal artery sections.17 Furthermore, the rarity of SCAD, coupled with overlapping symptomatology with other pathologies, complicates its diagnosis during pregnancy, putting the lives of affected women at risk.17 Despite considerable progress in understanding SCAD over the past decade, substantial gaps persist in establishing high-quality, evidence-based guidelines for optimal care.3,18,19 The current management strategies, primarily backed by low-level 12 evidence, emphasize a critical demand for more vigorous and comprehensive research.18,20 Moreover, there needs to be more research explicitly targeting young women aged 19-30, even though SCAD is increasingly recognized as a frequent cause of ACS among women.8 The clinical complexities SCAD presents, heightened by the diagnostic challenges, especially in younger females, amplify the necessity for dedicated research and awareness campaigns.18 Statement of the Problem According to recent epidemiological data, there has been a concerning increase in the incidence of AMI among young women, even in those without traditional cardiovascular risk factors.14,21 This shift in cardiovascular disease demographics highlights the need for further research, particularly in young women with SCAD. While numerous research efforts have investigated SCAD’s wide-ranging characteristics, data specific to women aged 19-30 remains essentially unexplored. As a result, there remains a lack of specific data regarding common contributing factors, challenges in diagnosis, optimal management strategies, and outcomes of SCAD in this demographic.21,22 This gap in knowledge heightens the risks of generalized approaches to diagnosis and management, which may not adequately address the unique needs and vulnerabilities of young women with SCAD.21,22 Therefore, it is crucial to bridge this gap in information to improve the understanding and management of SCAD in this population. Purpose of the Study The purpose of this qualitative analysis is to investigate the common contributing factors, diagnostic challenges, trends in management strategies, and outcomes of SCAD 13 in young women. Utilizing a case study design, this research examines the experiences and medical records of women aged 19-30 who have been diagnosed with SCAD. Case studies were drawn from various peer-reviewed and published works obtained using Google Scholar, PubMed, NIH, and Weber State University’s Stewart Library One Search. Through insights from these case studies, we aim to narrow the knowledge gap, bring essential attention to the occurrence of SCAD within this demographic, and advocate for the most effective approach to managing this disorder in young women. Furthermore, we hope to empower young women to actively advocate for their health, encouraging proactive patient-provider collaboration. Research Questions Q1. What are the common contributing factors for SCAD among young women in this age group? Q2. Are there specific challenges in diagnosing SCAD in young women, and if so, what are they? Q3. What treatment options are commonly utilized in young women with SCAD, and what factors impact the selection of these treatments? Q4. What are the short-term and long-term clinical outcomes for young women with SCAD, and what factors influence these outcomes? Nature of the Study Research Method and Design The purpose of this thesis is to consider and discuss the complexities of SCAD in young women aged 19-30 through a qualitative analysis. Recognizing the unique aspects of SCAD’s presentation regarding this clinical population, a case study design was 14 chosen as it provides an opportunity to gain a more comprehensive understanding of SCAD within a typical environment. Qualitative Research The qualitative method was chosen for its potential to support a detailed understanding of SCAD in young women. While quantitative studies predominantly offer statistical insights, qualitative research allows for a greater understanding of individual experiences, valuable given the unique circumstances and challenges associated with SCAD in young women. Case Study Design Case studies are particularly relevant when examining occurrences of SCAD within real-life settings. In this thesis, the case study design facilitates a multi-faceted investigation of SCAD by incorporating various perspectives. Variables and Constructs A more thorough discussion of the variables and constructs will appear in the Methods Chapter, however it’s important to emphasize that the principal constructs are the predispositions, clinical symptoms, associated risk factors, and outcomes of SCAD in young women. Data Collection and Analysis Data will be gathered through careful web-based searches via Google Scholar and Weber State University’s Stewart Library online database utilizing specific key words. This comprehensive search method provides an extensive sweep of the available literature, presenting both widely recognized conclusions and individualized insights. 15 For data analysis, a thematic analysis methodology was implemented, utilizing an iterative coding process which involved both authors performing multiple reviews of the data, refining codes and themes with each pass, allowing both scope and discernment in the acquired themes. Foundational Support This thesis utilizes a qualitative methodology, exploring case studies to reveal thematic insights.23 By integrating phenomenological principles, which prioritize the true fundamental nature of individual experiences over generalizations, with Colaizzi's structured methodology, this paper offers an intricate and thoughtful interpretation of the phenomenon.24,25 This combined approach emphasizes the connection between individual case nuances and the overarching phenomenon, emphasizing depth over breadth.23,25 Central to this is the hermeneutic circle, an iterative process that ensures the authenticity of the analysis, while capturing the genuine experiences reflected within the case studies.25,26 Significance of the Study SCAD, a serious cardiovascular condition, remains inadequately researched among young women despite growing awareness and its critical nature.27,28 This gap, especially concerning diagnosis, management, and long-term outcomes, draws attention to unmet clinical needs for this age group, whose unique physiological and hormonal profiles demand specialized consideration.27 Our study, utilizing thematic analysis of case studies, highlights the nuanced experiences of young women, often overlooked in broader quantitative studies. Additionally, it serves as a compensatory response to historical 16 biases favoring male-centered research, emphasizing the need for more gender-specific studies in cardiovascular research. Definition of Key Terms Spontaneous coronary artery dissection. A non-traumatic, non-iatrogenic separation of the walls of coronary arteries forming a false lumen. This separation can take place either between the innermost and middle layers or between the middle and outermost layers of the artery.29 Intramural hematoma. A blood-filled swelling inside the arterial wall. This swelling can press against and narrow the artery's main channel, reducing forward blood flow.29 Iatrogenic. Caused by a medical professional, treatment, or diagnostic process.30 Atherosclerosis. The narrowing or stiffening of arteries due to plaque accumulation on their inner walls.31 Myocardial ischemia. A condition where the heart muscle receives insufficient oxygen due to reduced blood flow to the heart.32 Acute coronary syndrome. A spectrum of conditions characterized by sudden and decreased blood supply to the heart, encompassing myocardial infarction and unstable angina.33 Myocardial infarction. the permanent damage or death of heart muscle cells due to an extended deprivation of oxygen (ischemia).34 Summary The prevalence of myocardial infarctions, especially SCAD, is notably rising among young women without traditional cardiovascular risks.1,35 While the recognition 17 of SCAD is growing, its indistinct and wide-ranging symptoms often lead to misdiagnoses, emphasizing the urgent need for greater accuracy in diagnosis and intervention.16,19 This qualitative thesis focuses on young women aged 19-30, a group generally under-researched, to provide deeper insights into SCAD’s experiences, challenges, and prevention strategies. Using a case study approach, this paper highlights the complexities of SCAD within this demographic, adding to the existing literature and promoting a refined strategy in managing SCAD. 18 Chapter 2: Clinical Background Introduction Spontaneous coronary artery dissection (SCAD) is defined as a non-iatrogenic separation in the coronary artery wall that occurs independent of atherosclerosis or trauma.1,2,4,5 Following an intimal tear or ruptured vasa vasorum, an intramural hematoma (IMH) develops, compressing the true lumen and ultimately leading to coronary artery obstruction and myocardial injury.2,5 SCAD is the leading cause of acute coronary syndrome (ACS) and sudden cardiac death in young people, particularly among young and middle-aged women, who lack traditional cardiovascular risk factors.1–3 According to recent studies, SCAD is responsible for myocardial infarction in up to 43% of women under the age of 50.36 Although the etiology of SCAD is not well understood, It appears to be strongly associated with pregnant and postpartum women, as well as individuals with underlying systemic inflammatory or connective tissue disorders.19 While our understanding of SCAD has evolved over the years, it remains a complex and challenging condition to study due to its diverse clinical presentation and the absence of definitive diagnostic criteria. Etiology SCAD is a distinct clinical entity from atherosclerotic ACS.4 In the general population, ACS primarily results from plaque rupture and superimposed thrombosis, however, in patients with SCAD, ACS occurs through the development of an intramural hematoma, compression of the true lumen, and subsequent distal coronary flow obstruction.1 While the exact cause of SCAD is unclear, research suggests that it is likely influenced by a combination of genetic, hormonal, vascular, and environmental factors.1,3 19 It predominantly affects young, pre-menopausal women, and has been associated with pregnancy and fibromuscular dysplasia (FMD).4 Fibromuscular dysplasia (FMD), a non-atherosclerotic, non-inflammatory systemic vascular disease, is the most common concomitant arteriopathy in patients with SCAD.1,5 It is characterized by fibrous dysplasia, most often medial fibroplasia, that leads to a disruption and reduction of smooth muscle cells (SMCs) and an accumulation of extracellular matrix (ECM).37–39 These structural changes can weaken the arterial wall, increasing the risk of dissection.39,40 Both FMD and SCAD disproportionately affect women and share a high prevalence of extracoronary vascular issues such as stenosis, aneurysms, dissection, and tortuosity.38 Given the histological and angiographic similarities between these two conditions, researchers have hypothesized that SCAD may be a coronary manifestation of FMD.1,5 Research into the genetic determinants of SCAD is in its early stages and is challenging due to the lack of a clear monogenic basis.3 Some known genes related to connective tissue disorders, such as Marfan syndrome and vascular Ehlers-Danlos syndrome, have been observed in SCAD patients, but only account for a small percentage of cases (≤ 9%).3,5 The increased prevalence of SCAD in women may be due to genderspecific genetic regulation, such as genes with estrogen response elements, or inherent gender-related differences in coronary biology, which extend beyond specific genes or genetic factors.3 Future research aims to identify genetic variants in specific subgroups, such as familial SCAD or recurrent cases.3 Additionally, genome-wide studies are being considered to uncover more risk-conferring genetic factors, but their clinical application remains uncertain.3 20 Influence of female sex hormones such as estrogen and progesterone may induce collagen degeneration and weaken the arterial walls, increasing the likelihood of rupture or dissection.1,2,19 Hemodynamic changes during pregnancy can increase the sheer stress within the arterial wall and may lead to the development of SCAD.2 SCAD can also be triggered by extreme physical or emotional stress, Valsalva-like actions, and the use of sympathomimetic medications.1,2 While most cases of SCAD can be linked to a predisposing factor or disease, up to 20% of cases cannot be associated with an underlying cause and are classified as idiopathic.4,41 Epidemiology The true occurrence of SCAD remains unclear due to its frequent underdiagnosis and misdiagnosis, especially in patients with low risk for atherosclerotic diseases.2,4,5 Accurate estimation of SCAD's incidence and prevalence is complicated by several factors, including the reliance on administrative databases, incomplete exclusion of atherosclerotic dissections, outdated diagnostic criteria, and the lack of data on patients who passed away prior to diagnosis or those without access to coronary imaging.3 Recent studies suggest that SCAD accounts for approximately 1% to 4% of ACS cases.2,3,5 It predominantly affects females between 45 and 53 years of age, without traditional risk factors for atherosclerotic disease, but is increasingly being recognized in older and postmenopausal women.1–3,5,41 SCAD may be responsible for up to 35% of ACS cases in women under 50 years old and approximately 43% of pregnancy-associated myocardial infarctions.2–5 Mortality rates associated with SCAD are relatively low, around 1-2%, with an estimated incidence of recurrent ACS at approximately 18%.1 While SCAD has been 21 reported in various racial and ethnic groups, it is most frequently documented in white patients, possibly influenced by referral and sampling bias, as well as the demographics of reporting centers.5 Pathophysiology The pathophysiology of SCAD is unclear; however, it is believed to involve an injury or spontaneous hemorrhage that disrupts the integrity of the coronary artery wall.1 This disruption results in the formation of an intramural hematoma (IMH) and separation of the layers of the coronary artery wall.3,42,43 Unlike typical dissections, SCAD is noniatrogenic and occurs independent of atherosclerosis or trauma.1,42 Two main theories have been proposed to explain the pathophysiological process of IMH formation in SCAD. The 'inside-out' hypothesis suggests that an intimal tear creates an entry point for blood to flow from the true lumen into the subintimal space, resulting in an IMH.39,40,42 The ‘outside-in’ hypothesis posits that the IMH arises de novo, possibly due to the rupture of small blood vessels within the coronary artery wall known as the vasa vasorum.39,40,42 When these arterioles rupture, blood pools within the intramural space and a hematoma forms.39,40,42 Regardless of the underlying mechanism, when the IMH expands, it creates a false channel (or lumen) that compresses the true lumen and obstructs coronary blood flow, leading to myocardial ischemia and infarction.1,2,39,42 Thrombus formation within the true or false lumen also plays role in the pathophysiological process of ACS in SCAD.2 Additionally, because SCAD patients typically lack coronary atherosclerosis or calcification, the IMH can propagate the dissection plane freely, resulting in more extensive dissections compared to cases of atherosclerotic plaque rupture.1,44 22 History and Physical The clinical presentation of SCAD varies and is largely dependent on the dissections location, size, and rate of progression.19,41 Approximately 90% of SCAD cases manifest with classic signs and symptoms of ACS including chest, shoulder, or epigastric pain, as well as nausea, vomiting, dyspnea, diaphoresis, and syncope.4,5,37,43 These patients frequently exhibit elevated troponin levels and ECG findings consistent with an ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI).1,3,44 SCAD patients can also present with ventricular arrhythmias, cardiogenic shock, or sudden cardiac arrest (<10%).4,19,41,43 Patients experiencing pregnancy-related SCAD often develop more severe clinical manifestations, including impaired left ventricular function, shock, and dissection in the left main or multiple vessels.42 Although rare, cases of asymptomatic SCAD have also been reported.45 Evaluation Prompt and accurate diagnosis of SCAD is crucial, as treatment strategies differ from those utilized in cases of atherosclerotic disease, and misdiagnosis can have serious adverse consequences for this patient population.36,46 Most acute medical services primarily prioritize identifying patients at high risk of obstructive atherosclerotic ACS, which can result in delayed diagnosis of SCAD.8 When evaluating patients presenting with signs and symptoms of ACS, demographics such as young age (≤50), female gender, and the absence of conventional cardiovascular risk factors should raise suspicion of SCAD.5,40 23 Coronary Angiography Coronary angiography is considered the gold standard diagnostic tool for patients with ACS and suspected SCAD, and should be performed as early as possible.5,46 The classic angiographic presentation of SCAD commonly features multiple radiolucent lumens that create a distinct beaded appearance within the affected artery, as well as extraluminal contrast staining or partial vessel obstruction caused by an IMH or dissection flap.1 However, these characteristic features are only present in a small percentage of cases, and their absence can result in underrecognition and misdiagnosis.2 To assist in the diagnostic process, SCAD has been categorized into three distinct angiographic types.40 The first type, known as type 1 SCAD, aligns with the classic presentation of the condition as previously described. The most common presentation, type 2 SCAD, is characterized as a prolonged and diffuse narrowing of the coronary artery, exceeding 20 millimeters in length, with varying degrees of severity.37,40 Within type 2 SCAD, two subtypes are identified: type 2A lesions have a gradual and prolonged narrowing, featuring an abrupt demarcation separating the affected segment from the adjacent, healthy artery; in contrast, type 2B SCAD initially appears normal but gradually tapers down in diameter as it extends distally, mimicking what might seem like 'normal tapering’.5,37 Type 3 SCAD presents a diagnostic challenge due to its close similarity to atherosclerotic disease.40 Notable distinguishing characteristics include the absence of atherosclerosis in other coronary arteries, the presence of relatively long lesions ranging from 11 to 20 mm, and a hazy appearance within the narrowed region.40 Additionally, this type of SCAD may manifest as either focal or tubular stenosis.5,40 Another variant of SCAD, known as type 4, has also been reported in medical literature, but is not frequently 24 encountered in clinical practice.2 It is characterized by complete vessel occlusion, resembling thromboembolic disease, and primarily occurs in the distal coronary artery segments.2,46 SCAD can occur any coronary artery but is most commonly observed in the LAD, often affecting the mid-to-distal segments and side branches.4,44 Approximately 50% of cases involve the LAD, while 30% occur in the circumflex (LCX), ramus, and obtuse marginals (OM), 35% in the right coronary artery (RCA) and its branches, and 4% in the left main coronary artery (LMCA).1 Multivessel SCAD occurs in anywhere from 9% to 25% of cases.1,5,44 Intravascular Imaging While coronary angiography has long been employed in the diagnosis of SCAD, it presents inherent limitations due to its reliance on two-dimensional lumenography, which solely focuses on the interior of the blood vessel and fails to capture detailed images of the arterial wall.5,43 This can make the diagnosis of SCAD challenging, especially in the absence of pathognomonic signs.43 To overcome these limitations, intravascular imaging methods like intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can be used to visualize dissection flaps, intramural hematoma, intimal tears, and both true and false lumens.1 By integrating these intravascular imaging modalities with angiography, clinicians can effectively diagnose SCAD cases that may not exhibit intimal rupture or present with ambiguous angiographic signs, as seen in type 2 and type 3 SCAD.37 However, careful patient selection and meticulous techniques are crucial when choosing intravascular imaging due to the 25 increased risk of dissection propagation and iatrogenic complications in patients with SCAD.36,44 Coronary Computed Tomography Angiography Although CCTA is not typically performed in the acute setting of ACS or SCAD, it can serve as a valuable non-invasive tool when proximal or large-diameter coronary arteries are affected.1,5 In such cases, CCTA can provide important diagnostic information and assist in patient follow-up and management.1,5 However, its utility may vary based on the extent and location of coronary artery involvement.5 When SCAD affects distal coronary arteries or small branches, or when there is minimal intimal disruption, CCTA’s diagnostic capabilities are limited and may produce false-negative results.1,5 Treatment / Management Options Managing SCAD presents a significant challenge due to the limited body of evidence available to guide clinical decision making.4 Current recommendations heavily rely on insights derived from patient series and expert opinions.9 The existing literature suggests various treatment strategies, including medical intervention, thrombolytic therapy, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG).19 Conservative Management Conservative management is the preferred treatment approach for patients who present with single vessel dissection and are clinically and hemodynamically stable.9,19 Research findings indicate that angiographic healing occurs in more than 90% of SCAD cases, typically within 30 days of initial presentation.4,9,44 However, it is not uncommon 26 for patients to experience recurrent MI due to dissection propagation, and may occur in approximately 5% to 10% of those managed conservatively, especially in the first week following an acute episode.4,5 Emergency revascularization is often required for these patients, with no identified angiographic or clinical indicators of acute deterioration.5 Based on these findings, it is recommended that patients be admitted for 3-5 days, and followed closely after discharge, to monitor for early signs of dissection extension or new recurrent SCAD.1,4,5,9 Revascularization Given that SCAD does not involve plaque rupture and thrombosis like atherosclerotic coronary artery disease, revascularization techniques such as Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Grafting (CABG) are generally not utilized in the management of stable patients.1 In cases of SCAD, PCI has been associated with increased risk of complications and less favorable outcomes.1 However, conservative management may not be suitable for high-risk patients who are clinically or hemodynamically unstable, experiencing ongoing ischemia, or presenting with LMCA dissection.5,40,44 In these cases, urgent intervention, such as PCI or CABG, should be considered.5 PCI is the preferred method for revascularization; however, it is associated with significant technical challenges and success rates below 50%.44 Guidewire navigation can be particularly difficult, presenting a high risk of hematoma propagation and iatrogenic injuries during angioplasty.5,44 In some cases, this can lead to further vessel occlusion, requiring emergency bypass surgery.1,5,44 Additionally, stenting may not be feasible in cases of distal, small caliber, or extensive artery dissections.40 Distal arteries 27 are often too small for stent implantation, and extensive dissections require longer stents, increasing the risk of restenosis.5,40,44 Drug-eluting stents may help mitigate this risk, however IMHs tend to resorb over time, which can lead to subacute and late strut malapposition, and an increased risk of very late stent thrombosis, especially after discontinuing dual anti-platelet therapy.5,40,44,47 If deemed necessary, stent implantation should be approached conservatively, prioritizing stent placement in the proximal segment.44 This will seal the dissection entry and help reduce the risk of hematoma propagation.44 Distal dissections tend to resolve as the IMH is reabsorbed, and typically do not require treatment as long as there is adequate coronary flow and no significant obstructions.44 To prevent hematoma propagation in longer lesions, a multistep approach can be utilized by stenting the distal and proximal edges first, followed by the middle dissection segment.40 Due to the limitations of coronary angiography, the use of OCT or IVUS is recommended for all PCIs to ensure proper stent coverage and apposition.40,44 CABG should be considered in patients with left main or proximal dissections, or refractory ischemia, as well as in cases where PCI has failed or is technically unfeasible.1,40,44 Apart from the inherent risks associated with surgical interventions during AMI, SCAD presents specifical technical challenges for CABG.3 The dissected coronary artery tissues are extremely fragile, making them unsuitable for sutures and highly susceptible to anastomotic complications, especially in patients with hereditary connective tissue disorders.3 Surgeons must therefore avoid bypassing directly onto dissected tissue, which may limit the feasibility of CABG in cases of distal vessel dissection.3 Additionally, follow-up studies report high rate of graft occlusion and failure 28 following CABG for patients with SCAD.1,3,44 This may be due to the increase in competitive flow as the native artery heals, or as a result of anastomotic complications.1,3,44 Regardless, CABG can be an effective temporary treatment option for patients with SCAD and should not be excluded based on these observations.3 It demonstrates excellent in-hospital outcomes and has a reported mortality rate of less than 2%.44 Medical Management Given the absence of randomized clinical trials, medical management strategies primarily rely on expert opinion.44 Patients are often initially prescribed a combination of anticoagulation, dual antiplatelet therapy, heparin, and beta-blockers to uphold the patency of the true lumen and mitigate the risk of thrombotic occlusion.1 However, it is important to acknowledge that while these medications fulfill their intended purpose, they may inadvertently impede the IMHs healing process and further contribute to dissection propagation.44 Current research does not strongly encourage the routine application of dual antiplatelet therapy in SCAD patients unless they have undergone PCI, in which case, the current guidelines recommend the administration of dual antiplatelets for a minimum of one year.1 Expert consensus often advocates for the long-term administration of aspirin, however, there is a lack of substantial data to support the extended use of antiplatelet therapy in SCAD.1 In addition, heparin should be discontinued once SCAD has been confirmed through angiography to reduce the risk of IMH propagation.1,40 Thrombolytic agents should be strictly avoided in the context of SCAD, as they have the potential to increase bleeding and exacerbate the IMH, leading to clinical deterioration and adverse outcomes.19,44 Thrombolytic therapy is also associated with an 29 increased risk of coronary artery rupture and the development of cardiac tamponade, which can have life-threatening consequences.1 Beta-blockers are advised for all patients, as they have been shown to diminish arterial shear stress, promote the healing process, and lower the risk of long-term recurrence.1,40,44 In cases where there's significant left ventricular systolic dysfunction (ejection fraction ≤40%), angiotensin-converting enzyme inhibitors (ACEIs) can be employed.1,40 Chest pain after SCAD can be caused by various factors, such as coronary vasospasm, microvascular diseases, or non-cardiac origins, and can result in frequent hospitalizations.1 These symptoms are typically managed with medications like nitrates, calcium channel blockers, or ranolazine.1 While nitroglycerin may provide relief during acute episodes of SCAD by addressing vasospasm, it is typically not recommended for long-term use.40 For patients with recurring symptoms, diltiazem can be an effective option.9 Complications SCAD is associated with a wide range of complications that can significantly impact patients' well-being and quality of life. These complications can vary depending on the initial treatment strategy. Immediate complications include ventricular tachyarrhythmias, ventricular free wall or septal rupture, congestive heart failure, cardiogenic shock, and cardiac arrest.1,4 Intermediate and long-term complications are common and may include chest discomfort, recurrent MI, unanticipated revascularization, stroke, and death.5,40 Approximately 20% of patients present with recurrent SCAD.1 30 During the first 7 days following SCAD, early complications such as recurrent MI may occur in up to 10% of conservatively managed patients, primarily as a result of dissection extension.48 The use of anticoagulants, antiplatelets, and thrombolytic therapy can exacerbate intramural bleeding and worsen IMH, leading to dissection extension, coronary artery rupture, and even cardiac tamponade.1,4 Additionally, PCI has been associated with less favorable outcomes and an increased the risk of complications including IMH and dissection propagation, iatrogenic dissection, abrupt vessel occlusion, in-stent restenosis, and stent thrombosis.1,3,48 Recurring or worsening angina, dynamic alterations in ECG readings, and elevated cardiac enzyme levels are all indicative of potential complications.49 Migraine headaches and mental health disorders such as post-traumatic stress disorder, depression, and anxiety are frequently observed in post-SCAD patients, and significantly impact their quality of life.1,3,48 Factors such as younger age, female sex, pregnancy-related SCAD, and lower resiliency scores are associated with a higher risk of developing psychological symptoms after SCAD.3 Moreover, patients with pregnancyrelated SCAD tend to present with more severe clinical manifestations, such as impaired left ventricular function, shock, and multivessel dissections, leading to larger infarcts and poorer clinical outcomes.3,4,40 Summary SCAD has emerged as a distinct and complex clinical entity within the domain of ACS.1 It predominately affects young women without traditional cardiovascular risk factors and has become increasingly recognized as a significant cause of ACS among this population.1,3,5 SCAD is responsible for up to 35% of ACS cases in women under 50 31 years old and approximately 43% of pregnancy-associated MI’s.50–53 While exact cause of SCAD is not fully understood, it has been linked to underlying arteriopathies, such as FMD, pregnancy, and the postpartum period, as well as potential triggers such as physical and emotional stressors and recreational drugs.4,5,19,41 Although the clinical presentation of SCAD often mimics atherosclerotic ACS, it possesses distinct underlying mechanisms and pathophysiological processes, and requires significantly different treatment strategies.1 Traditional approaches like PCI and thrombolytic therapy are inappropriate for SCAD and may even worsen the condition.36,46 Misdiagnosing SCAD can lead to treatment delays and suboptimal care, potentially resulting in adverse clinical outcomes.36,46 The management of SCAD is further complicated by the limited body of evidence available to guide clinical decision-making, as well as the lack of standardized diagnostic and treatment protocols.4 In light of these challenges, the accurate diagnosis and management of SCAD requires healthcare providers to maintain a high level of clinical suspicion when evaluating young women with chest pain and ECG or cardiac biomarker abnormalities.4,5,40 Further research and physician collaboration is essential to enhance our understanding of SCAD and improve patient outcomes. Establishing standardized diagnostic criteria and treatment guidelines will not only aid in prompt and accurate diagnoses, but also ensure that patients receive the most effective and personalized care possible. 32 Chapter 3: Literature Reviews Documentation We executed a systematic search for relevant case reports and research studies on SCAD in young women. Our main resources were Weber State University’s Stewart Library One Search, Google Scholar, NIH, and PubMed. The search was guided by key terms such as “Spontaneous Coronary Artery Dissection”, “intramural hematoma”, “iatrogenic”, “atherosclerosis”, and “myocardial ischemia”. Both authors engaged in an independent review of the identified studies to ensure alignment with our inclusion and exclusion criteria.54 The subsequent qualitative review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.55 To be included, case studies had to meet the following criteria: be peer-reviewed, published between 2010 and 2023, and focus on a young woman aged 19-30 with a confirmed SCAD diagnosis. General Literature Review Prevalence Since its initial identification in 1931, SCAD was considered a rare and often fatal contributor to ACS, MI, and sudden cardiac death in peripartum women.5 It's only in the last decade that SCAD has garnered increased recognition, primarily through academic initiatives, advanced cardiac imaging, and patient advocacy.15 These combined efforts have led to the realization that SCAD has been significantly underdiagnosed for many years, and its actual prevalence remains unknown.15,56 Accurately estimating the population-based occurrence of SCAD continues to present challenges due to a reliance on administrative databases, incomplete clinical data, difficulties in distinguishing it from 33 atherosclerotic dissections, outdated angiographic criteria, and a lack of data on deceased individuals and those without coronary imaging.3 As a result, reported prevalence rates vary widely throughout scientific literature. For instance, in a study from 2009, Vanzetto et al. reported a prevalence rate of 0.2% among 11,605 cases of ACS.57 In contrast, Clare et al. identified SCAD in 208 out of 26,598 AMI cases between 2006 to 2016, reporting a prevalence rate of .78%.58 Furthermore, the use of optical coherence tomography (OCT) for SCAD diagnosis has been shown to yield significantly higher prevalence rates.40 In 2016, Nishiguchi et al. reported a prevalence rate of 4% when employing OCT.59 These variations not only highlight the disparities in epidemiological reports but also underscore the substantial influence of diagnostic techniques when estimating the prevalence of SCAD. Increased prevalence rates are also frequently reported among female ACS patients. For example, a study using data from the National Inpatient Sample between 2009 and 2014 reported SCAD in 0.98% of 752,352 women diagnosed with AMI.3,60 When exclusively examining female patients, Vanzetto et al. reported a significant increase in prevalence from 0.2% to 1.2%.57 Their study also revealed an inverse relationship between SCAD prevalence and patient age, reporting prevalence rates of 2.1%, 4.0%, and 7.6% in women less than 60, 50, and 40 years old, respectively.57 Additionally, the prevalence of SCAD increased to 8.7% in women under 50 years old with ACS and 10.8% in the presence of ST-segment elevation.57 As the accuracy of SCAD diagnosis has improved over time, recent studies have reported an even higher prevalence in women under 60 years old presenting with MI.56 In 2014, Saw et al. identified SCAD as the underlying cause of MI in 24% of women under 34 50 years old.61 Subsequently, in 2016, another study reported SCAD as the cause of MI in a remarkable 35% of women under the age of 50.62 Patient Characteristics Research has consistently shown that women are more likely to be affected by SCAD, accounting for up to 95% of cases.3,56–59,63,64 While SCAD has historically been associated with young women, recent studies reveal that the average age of female SCAD patients typically falls within the range of 44 to 53 years.3,27 For example, in a retrospective cohort study by Clare et al., SCAD patients were predominantly women, constituting 88.9% of the cohort, while only 31.6% of non-SCAD patients were female.58 SCAD patients were also found to have a mean age of 49.0 years, which was considerably younger than non-SCAD patients, who averaged 65.6 years.58 Similarly, a 2015 case series by Yip and Saw reported an average age of 52.1±9.2 years, with 58% of participants aged 50 years or older, and 62.3% in the post-menopausal stage.40 Although SCAD occurs across all racial and ethnic groups, there is a large discrepancy in case reports and studies. The majority of SCAD patients reported in large case series (>80%) are described as being white, Caucasian, or of European origin.3,5,15,28,56,58,60,63,65,66 While it is possible that the pathophysiology of SCAD may have racial or ethnic biases, current evidence suggests that certain populations may just be under-represented in registry data.3,5,58 This is highlighted by a 2019 case series consisting of 45% Hispanic Americans and 16% Blacks, representing the most racially and ethnically diverse population-based cohort to date.3,58 When compared to other series of predominately white patients, this cohort exhibited remarkably similar presentations and outcomes despite differences in racial and ethnic demographics.3,58 These finding 35 suggest that rather than being at a lower risk for SCAD, certain populations are underrepresented in registries.3 This may be a result of referral and sampling biases, patient demographics near reporting centers, and healthcare and research accessibility.5,27 SCAD is often described as a condition that primarily affects individuals with few or no classic modifiable cardiovascular (CV) risk factors.15 However, recent findings have indicated that SCAD patients may have a higher burden of CAD risk factors than previously reported, with the prevalence of some, particularly hypertension and hyperlipidemia, closely resembling that of age and sex-matched populations.3,15 For instance, in a study of 327 SCAD patients, a relatively low prevalence of CV risk factors was observed, except for hypertension and dyslipidemia, which were present in 36.4% and 25.7% of patients, respectively.28 Similarly, a study by Tweet et al. reported a low prevalence of diabetes mellitus (0.4% to 4%) and current tobacco use (0%-0.7%), as well as an average body mass index of 25-26 kg/m2 ± 5 among female SCAD patients (n=323).66 However, chronic hypertension and hyperlipidemia were reported in 26% to 28% and 26% to 37% of patients, respectively, and a history of tobacco use was reported by 22% to 27% of patients.66 Furthermore, a comprehensive systematic review conducted in 2022 by Neubeck et al., identified hypertension as a predominant risk factors for SCAD, affecting 1,182 out of 3,729 patients across 23 studies.65 In this review, overweight and obesity were also identified as potential risk factors, with four studies reporting rates of 22.2% to 27% for overweight patients, and 11.8% to 33.3% for obese.65 Despite the potential association between SCAD and certain CV risk factors, SCAD patients often exhibit lower rates of these factors when compared to non-SCAD patients with ACS.58–60 For example, Clare et al.'s 2019 study revealed significantly 36 lower occurrence rates of CV risk factors in SCAD patients, along with fewer comorbidities, such as congestive heart failure, chronic obstructive pulmonary disease/asthma, history of stroke, history of acute myocardial infarction, and atrial fibrillation, when compared to non-SCAD pateints.58 Additionally, a population-based analysis by Mahmoud et al. showed that, on average, women with SCAD were younger and had fewer CV risk factors than their non-SCAD counterparts.60 Predisposing Factors Pregnancy-Related SCAD Pregnancy and the postpartum period have been identified as potential risk factors associated with the development of SCAD.48 Notably, Pregnancy-Related SCAD (PSCAD) accounts for up to 17% of all SCAD cases and is recognized as a significant cause of acute AMI during pregnancy, with an incidence ranging from 14.5% to 43%.3 Current estimates suggest that P-SCAD affects approximately 1.81 out of every 100,000 pregnancies.3 Women diagnosed with P-SCAD are, on average, between the age of 33 to 35 years old.5,67,68 Sheikh et al. reported that the average age at presentation for P-SCAD was notably lower than that reported for SCAD in general, at 32.62 years.67 Similarly, Tweet et al. identified a mean age of around 33 years.68 Additionally, women with PSCAD are often older at the time of their first childbirth and have a history of multiple pregnancies.3 In a retrospective study conducted by Chen et al., the average age of presentation was significantly lower in women with P-SCAD than those without (37.1 ± 5.7 vs 50.9 ± 9.9). However, despite being comparatively younger at presentation, the PSCAD group exhibited a high prevalence of advanced maternal age (68.2% > 35 years).69 37 They also exhibited higher rates of multigravidity compared to their Non P-SCAD (NPSCAD) counterparts (54.6% vs 31.4%).69 SCAD has the potential to affect women at various stages of pregnancy, as well as nulliparous and post-menopausal women. Nevertheless, findings from a 2010 prospective study indicate that P-SCAD primarily manifests in multiparous, high-risk women, particularly within the first month following childbirth (70%).3,48,70 These finding were corroborated in a subsequent literature review by Sheikh et al. (2012), which reported that 77% of P-SCAD cases between 1952 and 2010 occurred postpartum, while the remaining 23% took place during gestation.67 Demographic and comorbid conditions associated with P-SCAD include black ethnicity, advanced maternal age, age at first childbirth, chronic and gestational hypertension, lipid irregularities, migraines, chronic depression, preeclampsia, and infertility treatment.5,15,48,68 Sharma et al. observed significantly higher rates of postmenopausal hormone replacement therapy (HRT), previous fertility treatments, and pregnancy-related complications such as pre-eclampsia, gestational hypertension, and miscarriage in women with P-SCAD when compared to national averages.15 Similarly, Tweet et al. reported a greater prevalence of fertility treatments and pregnancy complications, including pre-eclampsia, in P-SCAD patients than in individuals with SCAD unrelated to pregnancy.68 Moreover, in Chen et al.'s retrospective study, 36.4% of P-SCAD patients exhibited high-risk features during their pregnancy, including gestational diabetes, hypertension, and pre-eclampsia.69 The relationship between sex hormones and the development of SCAD is supported by its higher prevalence in females and its association with pregnancy.71 38 However, the exact mechanisms of how hormonal levels and their fluctuations contribute to SCAD's development are unclear.3,71 Estrogen and progesterone, both of which increase during pregnancy, are believed to be key players in SCAD events in pregnant and postpartum women.3,5 These hormones may induce structural changes in the coronary arteries, making them more susceptible to SCAD.5,71 Progesterone can alter the shape and flexibility of elastic fibers in the arterial wall and reduce components of the extracellular matrix that support vascular cell health, thus weakening the vessel structure.71,72 Estrogen, conversely, promotes the activity of matrix metalloproteinases, enzymes that degrade proteins in the matrix surrounding cells.71,72 This can lead to cystic medial necrosis, where the middle layer of the blood vessel wall degenerates, forming cyst-like spaces and weakening the vessel walls.72 Estrogen can also compromise the structural integrity of the vasa vasorum at the media-adventitia border.72 These changes can accumulate over multiple pregnancies and cause progressive degeneration of the vessel wall.17 This explains why multiparous women are believed to be at an increased risk of SCAD.17,69 Moreover, pregnancy and labor impose additional hemodynamic stress on the circulatory system.72 This increased pressure can cause the vasa vasorum in the adventitial layer to rupture, leading to IMH, further weakening the vessel wall, and potentially causing dissection and its propagation.72 These changes, influenced by hormonal shifts and stressors, highlight the complex interplay of factors in the development of SCAD during pregnancy. 39 Exogenous Hormones Exogenous hormones, including oral contraceptives and hormonal replacement therapy (HRT), have also been suggested as potential risk factors for SCAD.18,48,73 The pathophysiological mechanism underlying SCAD development in this context is believed to involve heightened metalloproteinase enzymatic activity, leading to increased vascular remodeling, similar to the process observed during the peripartum period.48,73 Additionally, estrogenic conditions and HRT in postmenopausal women are known to exert significant effects on various physiological processes, including coagulation, arrhythmogenesis, vasomotor regulation, and oxidative stress, all of which can increase the risk of developing SCAD.48 However, direct evidence linking these factors to SCAD is somewhat limited, primarily relying on case reports and a single-center study.48 Oral contraceptives, while not considered causative, have linked to the development of SCAD in conjunction with concurrent vascular pathologies.48 Specifically, estrogen-containing oral contraceptives have been confirmed to increase SCAD risk, but the effects of combined hormonal therapy remain controversial.48 In a 2014 study, Saw et al. found no statistically significant link between the use of combined oral hormonal therapy and SCAD.48,74 Moreover, in a 2012 study, Tweet et al. identified hormone therapy as a potential precipitating factor for recurrent SCAD in some patients.68 This association was further highlighted in a 2021 retrospective study by Antonutti et al., revealing that 50% of patients with recurrent SCAD had a history of hormonal therapy.75 Several other cases have also reported a link between SCAD and exogenous hormones; however the rates of 40 contraceptive and HRT utilization among women with SCAD do not appear to significantly deviate from those in the general population.3 Fibromuscular Dysplasia Research consistently reports an association between FMD and SCAD, with a prevalence ranging from 25% to 86%.5,9,38,48,66,76 Data derived from the U.S. FMD Registry indicates that over 40% of recorded FMD cases report at least one occurrence of aneurysm or dissection, and about 25.7% reported multiple arterial dissections.5,38 In 2014, Saw et al. reported a strong association between FMD and SCAD, finding FMD in 72% of 168 patients with SCAD.40,74 72.7% of patients with FMD were found to have renal artery involvement, 50.4% had iliac arterial involvement, and 52.1% had cerebrovascular involvement.74 Similarly, Hassan et al. reported the presence of extracoronary FMD in 75.6% of their patient population.77 In 2012, the Mayo Clinic reported iliac arterial involvement in 50% of SCAD patients in retrospective series.40,68 In a more recent study, Sharma et al. also reported the presence of extracoronary FMD in 53% of SCAD.15 Additionally, McNair et al. found FMD in 63% of 51 female SCAD patients.78 Interestingly, they also observed that patients with FMD were significantly older at presentation that patients without FMD.78 They theorize that this may be due to a lack of angiographic evidence of FMD in younger patients with SCAD, which may develop later in life.78 In contrast, a US national population-based cohort study comparing SCAD and non-SCAD ACS patients from 2004 to 2016 reported FMD in only 0.16%.48 However, the wide range of reported rates is likely due to differences in the population, number of vascular beds imaged, and the modality and extent of screening.5,9 Vascular Abnormalities 41 Coronary artery tortuosity and extracoronary vascular arteriopathies including tortuosity, dilation, aneurysm, and dissection are also commonly observed in patients with SCAD.27 It is estimated that female SCAD patients are 4x more likely to have coronary artery tortuosity compared with matched controls.27,79 Various mechanisms have been proposed to explain how coronary artery tortuosity influences the development of SCAD, including changes in vessel structure and blood flow dynamics.79 In order for coronary tortuosity to develop there must be a disruption in the equilibrium between vessel traction, intraluminal pressure, and retractive forces that leads to vessel elongation. Elastin is essential for maintaining the structural strength and stability of arterial walls and is responsible for its load-bearing properties.79 Consequently, an elastin deficiency can make arteries more susceptible to elongation and tortuosity, as well as conditions like aortic aneurysms and dissection formation.79 Research has also demonstrated that an elastin deficiency can lead to the proliferation of smooth muscle cells in the subendothelial layer.79 Furthermore, disturbances in blood flow caused by sharp bends in tortuous vessels can disrupt laminar flow and increase shear stress on the vessel wall.79 This process can weaken the vessel wall, making it more susceptible to dissection.79 Interestingly, recurrent dissections tend to occur within these tortuous segments, raising the question of whether tortuosity is a marker of SCAD or if it predisposes patients to arterial fragility.80 Eleid et al. reported coronary tortuosity in 78% of SCAD patients, as well as significantly higher tortuosity scores when compared to the control group.79 70% of these patients also had evidence of extracoronary vasculopathy, most commonly FMD (80%).79 Moreover, severe tortuosity was identified as the only significant predictor of SCAD 42 recurrence.79 McNair et al. reported tortuosity in any non-SCAD coronary artery in 76% of patients, as well as non-coronary, non-FMD vascular abnormalities in 70% of patients.78 Similarly, in 2015, Prasad et al. reported non-coronary, non-FMD vascular abnormalities in 66% of SCAD patients at the Mayo Clinic SCAD Clinic from February 2010 to May 2014.81 In 2019, Sharma et al. found non-FMD vascular abnormalities such as beading, dissection, ectasia, aneurysm, and tortuosity in 100% of SCAD patients.15 The most commonly affected arteries were iliac, occurring in 82%, followed by renal, celiac, superior mesenteric, cervical or cerebral, and splenic arteries, at 74%, 53%, 35%, 29%, and 9%, repectively.15 Neurological Factors Migraines are a common comorbidity in patients, especially women, who have had ACS associated with SCAD.63 According to cohort studies, up to 46% of SCAD patients suffer from migraines, nearly double the lifetime prevalence of migraine in US women with stable angina (24%).63 In a 2014 study by Saw et al., 37.5% of SCAD patients reported having a history of migraines.74 Similarly, Kok et al. reported a lifetime prevalence of 40% among 585 SCAD patients and a 42% prevalence when adjusted for female patients only.63 When compared to the migraine prevalence in the general female population, they revealed that SCAD patients had an approximately 37% higher ageadjusted one-year migraine prevalence.63 Migraine headaches have also been linked to various vascular events, including cervical and vertebral artery dissections, aneurysms, reversible cerebral vasoconstriction, retinal vasculopathy, myocardial infarction, and stroke.63 There is also an association between migraines and FMD, with reported prevalence rates exceeding 30%.63 43 Notably, Kok et al. reported that 58% of SCAD patients with migraines also had FMD, and 23% exhibited arterial aneurysms, pseudoaneurysms, and dissections.27 Additionally, individuals with migraines and FMD may face a heightened risk of recurrent SCAD.58 Using cox regression models, Clare et al. discovered that FMD increased the incidence of recurrent SCAD by 5-fold, while migraines increased the risk by 3.4 fold.58 The observed relationship between SCAD, migraine headaches, and FMD may support the theory that these conditions are manifestations of systemic vascular abnormalities and have a susceptibility to injury throughout different vascular regions.58 Furthermore, Kok et al. suggests that while specific baseline vascular characteristics may be influential in conditions like SCAD, there are likely other significant factors at play, particularly hormonal changes in women.63 This is highlighted by the connection between migraine headaches and the menstrual cycle, as well as the association between hormonal fluctuations and SCAD.63 Migraine headaches are associated with the menstrual cycle in over 50% of women, with migraines without aura notably increasing in frequency in correlation with the decrease in estrogen and progesterone that precedes menstruation.63 A decline in hormonal levels has also been proposed as a potential triggering factor for conditions such as post-SCAD chest pain and pregnancy-associated SCAD, which predominantly occurs in the initial weeks following childbirth.63 Rheumatological and Systemic Inflammatory Diseases SCAD may also be associated with rheumatological and systematic inflammatory diseases. Infiltrated eosinophils are frequently found in the adventitia of dissected arteries in SCAD patients.9 Anatomopathological studies have validated the existence of 44 periarterial eosinophilic infiltrate in SCAD patients, while also verifying its absence in cases of iatrogenic or traumatic dissections.82 Whether this phenomenon is a consequence, or a cause of SCAD remains uncertain.9 Various case reports have documented occurrences of SCAD in the context of conditions such as lupus, antiphospholipid syndrome, systemic vasculitis, and other autoimmune disorders.83 Autoimmune disease has been reported to occur in 3% to 9% of SCAD patients.83 However, existing evidence does not account for the prevalence of autoimmune diseases in the general population, and therefore, the observed connections may be purely coincidental.83 A national survey revealed that SCAD is most commonly associated with autoimmune conditions like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Crohn's disease (CD).2 However, because rare cases like these are underreported, and physicians often encounter diagnostic challenges when identifying such associations, the available literature remains limited.84 SLE may play an important role in the etiology of SCAD, possibly due to a similar inflammatory pathophysiology to vasculitis.82 When compared to age-matched control groups, patients with SLE are 50x more likely to have coronary artery disease.82 Additionally, SLE is estimated to occur in 0.2 to 0.42% of SCAD patients.48 In a 2019 systematic review, Ullah et al. observed SLE in 60% of SCAD patients, as well as rheumatoid arthritis (RA), Crohn disease (CD), and other inflammatory diseases in 10% of patients.84 However, after age, sex, and county matching, and adjusting for race and BMI, Chaaban et al. found no evidence of an association between SCAD and autoimmune disease.82 Due to the limited data and lack of randomized trials, an association between SCAD and rheumatologic and inflammatory conditions cannot be confirmed.82 45 Genetic Factors Associations between SCAD and heritable connective tissue disorders such as Ehlers-Danlos syndrome (EDS), Marfan syndrome, Loeys-Dietz syndrome (LDS), and Pseudoxanthoma elasticum, as well as Autosomal Dominant Polycystic Kidney Disease (ADPKD) have been reported, but are relatively rare, occurring in only 5%-9% of patients.9,48 While the exact nature of this association is not well understood, it is important to acknowledge the potential significance of genetic factors in the development of SCAD. A gene sequencing study published in 2020 revealed that SCAD patients possessed rare genetic variants with a confirmed or putative pathogenic nature.85 These variants were predominantly found in genes linked to established disorders such as vascular Ehlers-Danlos, Loeys-Dietz, or adult polycystic kidney disease.85 Another recent population-based cohort study of 66,360 SCAD patients in the United States reported EDS and MFS in 0.02%, and ADPKD in 0.09% of patients.48 Nonetheless, it's important to consider that the reported rates could be underestimated due to the relatively low prevalence of these diseases, emphasizing the need for additional research to explore their potential connections with SCAD.48 EDS is a group of connective tissue disorders with diverse clinical characteristics, such as skin fragility, hyperextensible skin, and joint hypermobility.86 These disorders are categorized into fourteen distinct types based on clinical and genetic variances.86 Notably, some forms of EDS may lead to systemic effects, including vascular and cardiac involvement, affecting the heart, valves, and great vessels, potentially causing cardiac complications.86 Vascular complications are a significant source of morbidity and mortality in EDS patients, especially in those diagnosed with types I, IV, and VI.86 In 46 some cases, SCAD has been identified as the initial manifestation of undiagnosed EDS.48 Type IV EDS, or Vascular Ehlers-Danlos Syndrome (VEDS), appears to have a greater predisposition for SCAD than other types of EDS.48 VEDS is linked to mutations in the COL3A1 gene, which results in a type III collagen deficiency, a crucial component of blood vessel and hollow organ walls.87 This deficiency causes significant fragility in the vascular and gastrointestinal systems, often leading to the spontaneous rupture of major arteries and veins, as well as the uterus or bowel.87 Most patients present with arterial dissection or organ rupture by age 20, and 90% experience a significant spontaneous complication by age 40.88 ADPKD is the most common hereditary kidney disorder and has been known to present with various extrarenal manifestations, including hepatic, pancreatic, seminal vesicle and arachnoid cysts, cardiac valvular abnormalities, colonic diverticula, and bronchiectasis.89–91 It is recognized as a predisposing factor for vascular abnormalities, most often observed as subarachnoid cerebral aneurysms (5%-10%).90,91 While uncommon, aneurysms and dissections have also been reported in other locations, such as the thoracic aorta, and cervicocephalic and coronary arteries.89,91,92 Cardiovascular disease is the leading cause mortality in ADPKD patients, accounting for 36% deaths.89,92 ADPKD patients typically develop hypertension at an earlier age than the general population, even before kidney function impairment, likely due to disruptions in the renin-aldosterone system and endothelial dysfunction associated with impaired nitric oxide release.89,92 At this time, it is unclear whether arterial dissection in ADPKD is an extrarenal manifestation of the condition or primarily a consequence of hypertension.92 As of 2019, only eight cases have reported an association 47 between SCAD and ADPKD patients and due to its rarity, the exact prevalence of SCAD in individuals with PKD remains unknown.90,93 ADPKD is primarily caused by mutations in the PKD1 and PKD2 genes, which code for polycystin 1 and polycystin 2, two proteins that are essential for the development and maintenance of the vascular system, particularly in the tunica media.48,89,90,93 A 2000 study showed that reduced polycystin expression can weaken arterial walls and lead to rupture and hemorrhage.48 Additionally, localized defects in the media of extracranial arteries were observed in a 2012 autopsy analysis, indicating early stages of aneurysm development.89 These findings suggest that mutations in PKD genes may contribute to the vascular abnormalities associated with ADPKD, including SCAD.89 The PHACTR1 locus has emerged as a potential genetic factor linked to SCAD and FMD. Combaret et al. confirmed the genetic association of the PHACTR1 locus with SCAD, and Adlam et al. identified a genetic correlation between fibromuscular dysplasia and SCAD, specifically implicating the rs9349379 alleles of PHACTR1.94 While murine models by Rubin et al. did not find a causal relationship between PHACTR1 function loss and vascular pathology, research conducted by Wood et al. suggested a correlation between PHACTR1 loci and variations in the distensibility of certain arteries.94 Additionally, migraine headaches, known for their association with various vascular phenomena, have also been linked to PHACTR1 and share overlapping loci with cervical artery dissection, further emphasizing the intricate genetic associations among SCAD, FMD, and migraines.63 Investigations into the genetic factors of SCAD are still in the early stages.3 While heritable vascular disorders demonstrate a distinct multigenerational autosomal dominant 48 inheritance pattern, SCAD lacks a clear monogenic basis or strong familial pattern beyond its association with known genetic disorders.3,5 Moreover, the current body of genetic research has yet to provide a comprehensive understanding of the factors contributing to sex differences in SCAD susceptibility.3 Continued research and collaboration within the scientific community are essential for unraveling the complex genetic landscape of SCAD and developing targeted approaches for diagnosis and treatment. Mental Health The recognition of psychiatric conditions as independent risk factors for adverse cardiovascular events has increased in recent years.15 SCAD patients frequently experience symptoms of anxiety and depression, especially young women and individuals with peripartum SCAD.15 Psychiatric conditions may initiate various stressinduced physiological responses, potentially contributing to elevated shear stress and an increased risk of dissection.15 Women, particularly those with SCAD, may exhibit heightened susceptibility and more notable reactions to these physiological responses.15 A study by Murphy et al. revealed that patients with SCAD were more likely to report a history of anxiety or depression than their non-SCAD counterparts (48.6% vs 17.3%; 40% vs 22.8%).95 Additionally, over 50% of SCAD patients reported a history of any mental health condition.95 In contrast, a study conducted by Smaardijk et al. demonstrated lower levels of anxiety and depression in women with SCAD when compared to women with typical ischemic heart disease.96 However, they did observe heightened levels of perceived stress and fatigue among female SCAD patients prior to 49 SCAD events.96 Furthermore, a significant prevalence of burnout, reaching 20%, was also noted, slightly surpassing the population-based estimates of 17%.96 There appear to be significant gender-specific differences in the relationship between mental health and heart disease, particularly in cases of SCAD.15 Sharma et al. found that women reported a higher prevalence of anxiety and depression prior to SCAD events when compared to men.15 Specifically, 32% of women reported anxiety and 20% reported depression, while no male subjects reported a history of either condition.15 Similarly, a larger study by McAlister et al., revealed higher rates of depression, 20.2%, in female SCAD patients, compared to 9.8% in males.15 More women also reported a history of anxiety (17.5% versus 9.8%), but this was not found to be significantly higher than men.15 These differences reflect the gender disparities in depression prevalence across the general population, with depression being 1.6 times more prevalent in women than in men.94 There is also evidence of a relationship between migraines, mood disorders, and SCAD. Research indicates a significant association between migraines and an increased prevalence of mood disorders, as well as greater migraine-related disability when accompanied by depression.63 Moreover, anxiety and depression, as previously noted, are recognized as risk factors for cardiovascular disease.63 In a comprehensive study by Saw et al., baseline data revealed an increased prevalence of migraines (32.5%), depression (19.5%), and anxiety (19.7%) in patients with SCAD.56 Similarly, a Mayo Clinic series of 586 patients demonstrated a significant prevalence of migraines (40% lifetime, 27% 1year) in those with SCAD, with those experiencing migraines also reporting heightened levels of anxiety and depression.27,63 Kok et al.'s investigation further revealed elevated 50 rates of depression, as well as recurrent chest pain among SCAD patients with a history of migraines.63 Furthermore, Smaardijk et al. reported that participants with comorbid migraines exhibited increased symptoms of anxiety and fatigue compared to individuals without migraines (19% vs 5%).96 Their findings also revealed a higher prevalence of chronic fatigue syndrome (16% vs 1%) and moderate or severe depressive symptoms in female SCAD patients with FMD compared to those without FMD.96 Precipitating Factors Emotional and Physical Triggers Certain factors can act as triggers for an intimal tear or IMH in individuals at risk of SCAD, especially those with underlying predisposing arteriopathies.13,40,42 Extreme emotional and physical stress are the most commonly reported precipitators of acute SCAD events.13,42 Emotional stress can include the loss of a loved one, divorce, arguments, and job-related stress, while physical stressors typically include isometric exercise, such as weight lifting, or Valsalva-like activities such as childbirth, coughing, retching, vomiting, and bowel movements.13,42,74,97 Research suggests that SCAD events in women are frequently associated with emotional stressors, while men with SCAD more often report physical stressors, specifically intense isometric exercise and weight lifting.5,42 While the specific pathophysiological mechanisms linking physical and emotional precipitants to SCAD events are not fully understood, it is believed that these processes involve a combination of mechanical and hormonal factors.97 One hypothesis suggests that stress-induced catecholamines may increase arterial shear stress, myocardial contractility, and/or induce vasospasm, ultimately leading to the rupture or disruption of 51 the intima or vasa vasorum.5,13,42 Additionally, intense exercise, especially isometric efforts, can transiently raise intrathoracoabdominal pressure, further increasing coronary shear stress.13,40,42,97 This, in combination with increased catecholamine release, may result in the onset of intimal tear and intravascular hemorrhage.97 Several studies have documented the presence of physical and emotional stressors prior to acute SCAD events.3,48,56,68,74,97 Emotional stress has been recognized as a significant precipitating factor, with a reported prevalence ranging from 26% to 40%, and up to 48% for female SCAD patients.27,48 Physical stress has also been identified as a precipitating factor in 16% to 24% of cases.48 In a study conducted by Saw et al., more than half of their patients (56.5% of 168 patients) reported precipitating stressors preceding their SCAD event, with 40.5% experiencing intense emotional stress and 24.4% engaging in exercise before the event.74 Notably, 12.5% of patients engaged in heavy lifting or isometric exercise the day of or before their SCAD event.74 Men, in particular, exhibited a higher prevalence of physical stressors, with 39% involved in intense isometric activities or using methamphetamines, compared to 10% of women.74 Similarly, Tweet et al. reported exercise as the primary precipitating stressor in men, with 44% of men participating in extreme physical activity prior to a SCAD event, versus 2.8% of women.68 Additionally, in a 2016 study, emotional and physical stress were reported in 26% and 16% of patients, respectively.48 Among those engaging in physical exercise before the event, 10% reported aerobic activity, while only 6% reported isometric exercise.48 This study also revealed that women with concomitant FMD experiencing precipitating emotional stress were more susceptible to acute SCAD events, 52 while men without FMD reported exercise as the precipitating stressor to their SCAD event.48 Recent studies by Saw et al. and Gurgoglione et al. also reported high rates of precipitating stressors in SCAD patients.56,97 In 2019, Saw et al. identified potential precipitating stressors in 66.4% of their patients, with emotional stressors reported by 50.3% of patients, and physical stressors and heavy isometric activities reported in 28.9% and 9.8% of cases, respectively.56 In 2023, Gurgoglione et al. revealed similar occurrence rates, with 64% of patients presenting with precipitating stressor, of which 48.4% were categorized as emotional triggers and 15.6% as physical triggers.97 Notably, women were more likely to experience emotional triggers, associated with chronic stress, higher levels of C-reactive protein (CRP), and increased circulating eosinophils.97 In contrast, patients with physical triggers were predominantly male and had worse cardiovascular risk profiles.97 These findings suggest distinct pathophysiological mechanisms underlying SCAD based on the presence and type of precipitating triggers.97 Moreover, previous research indicates that eosinophils play a role in SCAD development by fostering angiogenesis and heightening the susceptibility of the coronary artery tree to vasomotor disorders.97 Additionally, Ridker et al. found that elevated CRP levels predicted future CV adverse events.97 Based on this information, the authors hypothesized that in individuals with emotional triggers, the elevated prevalence of chronic stress and increased levels of CRP and circulating eosinophils may contribute to the initiation of coronary dissection.97 Furthermore, atherosclerosis-related ACS samples exhibit significantly lower occurrences of these precipitants when compared to SCAD, ranging from 8 to 17% for 53 emotional triggers and approximately 14% for physical triggers.98 However, variations in prevalence estimates stem from differences in measurement tools and definitions across studies.98 There is also a potential for recall bias and overreporting, especially in the context of a life-threatening event like SCAD in young and previously healthy individuals.5 Additionally, no case-control studies have systematically compared the roles of emotional and physical triggers in SCAD versus atherosclerosis-related ACS.98 Given the lack of objective data on the magnitude of precipitant exposure and the impact of recall bias, particularly in retrospective survey-based SCAD studies, careful interpretation is crucial.3,5 Recreational drug use, particularly cocaine and amphetamines, has been suggested as a potential trigger for ACS in patients with SCAD.39 As a sympathomimetic agent, cocaine increases inotropic and chronotropic responses, and stimulates alphareceptors resulting in vasoconstriction.99,100 This process can increase shear stress on the arterial wall and lead to coronary artery dissection.99,100 Additionally, cocaine exhibits a prothrombotic effect by increasing platelet activity and aggregation.99,100 Similarly, amphetamine-induced SCAD primarily relates to mechanisms of coronary vasospasm and platelet activation-mediated thrombus formation.99 Recreational Drugs Cocaine is known for its association with various cardiovascular conditions and has been linked to coronary artery spasm and atherosclerosis.99,100 Although rare, it is also a well-recognized cause of ACS in young adults.99,100 The first case of cocaineinduced SCAD was reported by Jaffe et al. in 1994.99,100 In 2001, Steinhauer and Caulfield documented the first fatal case of cocaine-induced SCAD, and, that same year 54 Gelfand et al. reported the first occurrence of cocaine-induced SCAD in the left main stem, extending to the LAD and LCX arteries.100 While instances of cocaine and amphetamine use have been reported in some SCAD cases, establishing a definitive cause-and-effect relationship requires further investigation.3,39 While these stressors play a role in some cases, their absence in others underscores our incomplete understanding of the complex pathophysiological processes involved in the development of SCAD.5,42 Continued research is imperative to unravel the intricate pathophysiological processes involved in SCAD development. Clinical Presentation SCAD patients can present with a wide range of signs and symptoms, influenced by factors such as the dissection's location, size, and rate of progression, as well as the extent of myocardial ischemia.17,19,41 However, the majority of patients, approximately 90%, present with ACS, with or without ST segment elevation, and elevated levels of troponin.37,51 The most prevalent symptom is acute, sudden onset chest pain, often described as oppressive or stabbing and localized in the anginal, substernal, retrosternal, or interscapular regions.17,49 The pain is typically intense, occasionally radiating to the left arm, neck, and jaw, and accompanied by sensations of paresthesia, dysesthesia, or pressure.17,49 Additional symptoms, including dyspnea, diaphoresis, nausea, and profuse sweating have also been reported.17 In a 2017 Canadian cohort, chest pain was reported by 96% of patients, with 49.5% experiencing radiating pain to the left upper limb.101,102 Other frequently reported symptoms included neck pain (22.1%), nausea or vomiting (23.4%), diaphoresis (20.9%), and dyspnea (19.3%).101,102 Similar findings were reported 55 by Sharma et al. in their 2019 study, with more than 90% of patients presenting with chest pain, 20% with nausea or vomiting, and 18% with dyspnea.15 The proportion of SCAD patients presenting with STEMI versus NSTEMI varies widely across studies, ranging from 26% to 87% and 13% to 69%, respectively.101,103 In a 2015 study, 93% of SCAD patients (124 out of 134) presented with ACS, and of those, 49% were categorized as STEMI and 40% as NSTEMI.64 Daoulah et al. reported similar rates of ACS, with 49% of patients presenting with STEMI and 46% with NSTEMI.104 Interestingly, researchers noted a similar median left ventricular ejection fraction (LVEF) between male and female SCAD patients, but observed significantly higher admission troponin levels in females compared to males.104 In contrast, Saw et al. observed larger decrepitates in ACS presentations, reporting NSTEMI in 74.3% of SCAD patients compared to only 25.7% with STEMI.28 Additionally, 21.8% of patients presented with a reduced EF (< 50%) and approximately 84% exhibited a left ventricular wall motion abnormality (hypokinesis, akinesis, or dyskinesis).28 More recently (2022), Inohara et al. reported STEMI and NSTEMI presentations in 31.2% and 69.8%, respectively. Notably, STEMI patients were younger and had a lower body mass index compared to NSTEMI patients.105,106 They also presented with a lower LVEF on average and were more likely to experience ventricular fibrillation or tachycardia.105,106 Furthermore, in a 2019 cohort, 29.7% of patients presented with STEMI, while 69.9% presented with NSTEMI.56 Troponin levels were also elevated in the majority of patients (97.6%), 25.6% had a reduced LVEF (<50%), and 82.3% exhibited a LV wall motion abnormality.56 While less frequent, SCAD presentations may also include hypotensive hemodynamic alterations, bradycardia, and/or ventricular arrhythmias (fibrillation or 56 tachycardia), as well as cardiogenic shock and sudden cardiac arrest.3,17 Based on current reports, approximately 3% to 11% of SCAD patients present with ventricular arrhythmias or sudden cardiac death, and up to 5% experience cardiogenic shock.49,101,103 In their 2012 study, Tweet et al. reported ventricular fibrillation or tachycardia in 14% of patients, predominantly associated with STEMI.9 Subsequent studies by Saw et al. in 2017 and 2019 documented slightly lower rates of ventricular arrhythmias at 8.9% and 8.1%, respectively.28,56 Furthermore, Sharma et al. reported cardiac arrest in 12% of SCAD patients, including 4% occurring out-of-hospital.15 Nakashima et al. documented cardiogenic shock or cardiac arrest in 16% of their patients, while Lettieri et al. reported cardiogenic shock and out-of-hospital cardiac arrest in 2.2% and 2.8%, respectively.62,64 Furthermore, P-SCAD is often associated with more severe clinical presentations, including a higher prevalence of STEMI and reduced LVEF.15,49 In a 2017 study, Tweet et al. found that patients with P-SCAD were more likely to present with STEMI and acute heart failure compared to those with SCAD unrelated to pregnancy (NP-SCAD).66 In their cohort, STEMI was reported in 56% of P-SCAD patients and only 36% of NPSCAD patients.66 Additionally, LVEF was lower in patients with P-SCAD on average, and they were more likely to have an LVEF ≤35%.66 In contrast, Chen et al. observed similar rates of STEMI and ventricular arrhythmias between P-SCAD and NP-SCAD patients.69 However, like Tweet et al., they noted significantly lower LVEF at presentation.69 Moreover, cardiogenic shock and/or the need for hemodynamic support via an intra-aortic balloon pump (IABP) were more common in the P-SCAD group.69 Notably, the rates of ventricular arrhythmia, cardiogenic shock, and mechanical circulatory support were significantly lower than 57 those reported in previous studies (4.6% vs 9%-16%, 9.1% vs 20%-24%, and 9.1% vs 28%, respectively).69 These discrepancies could stem from the comparatively lower prevalence of STEMI and left main coronary involvement in this cohort or from ascertainment and publication bias, with more intricate cases often reported from tertiarycare centers.69 Additionally, the increasing volume of SCAD research over the past decade may have led to earlier recognition and improved care, potentially reducing adverse outcomes.69 The coronary distribution in SCAD appears to closely resemble that seen in atherosclerotic disease.80 The LAD is the most commonly affected artery, accounting for approximately 32% to 46% of cases, followed by the RCA (21.7–35.7%), and the LCX (9.6–19%).5,58,64,68,74,94 In some series, LAD involvement has been reported at even higher rates, up to 70.5%.62,76,107 Additionally, the LMCA is less frequently affected, with most reports documenting it’s involvement in ≤ 4% of cases.1,5,74,107 Saw et al. (2014) observed LAD dissections in 41.7% of patients, as well as involvement of the diagonal and septal arteries in 12.5%.74 Additionally, the branches of the circumflex artery were affected in 33.7% of cases, while the right coronary artery branches were involved in 21.4% of cases.74 The incidence of LMCA dissection was only 1.2%.74 In a more recent study (2021), Daoulah et al. reported LAD, RCA, and LCX involvement in 43.4%, 21.7%, and 9.6% of patients. Notably, 12% of patients also experienced LMCA involvement, which is significantly higher than previously documented rates.104 Furthermore, McAlister et al. conducted a study comparing coronary vessel distribution in male and female SCAD patients. They revealed a higher prevalence of LCX dissections in men (44.4% versus 30.9%) and RCA dissections in women (21.7% versus 11.8%), suggesting a potential 58 gender-based difference in the distribution of coronary vessel involvement in patients with SCAD.107,108 However, Daoulah et al. did not observed any significant difference in coronary distribution between male and female patients.104 Further research and analysis would be valuable to explore the implications of gender-specific patterns in coronary vessel involvement in SCAD patients. SCAD has also been shown to have a predilection to mid and distal artery segments.15,74,109,110 In a study by Saw et al. (2014) SCAD was more likely to affect the mid to distal sections of coronary arteries, with only 8.3% of their cases involving the proximal segments of the LAD, LCX, or RCA.74 Similarly, Sharma et al. observed dissections in the proximal, mid, and distal segments of the LAD in 12%, 29%, and 31% of patients, respectively.15 In contrast, findings from a study conducted by demonstrated that approximately 46.9% of LAD dissections occurred in the proximal segment, 37.0% in the middle segment, and 16.1% in the distal segment.74,111 In another study by Tweet et al., SCAD lesions were more prevalent in the mid artery segments (54%), followed by the distal (27%), proximal (17%) and ostial (2%) segments.110 These variations among studies may indicate some heterogeneity in the distribution of SCAD within coronary artery segments, emphasizing the need for further research to elucidate the factors contributing to these differences and their potential implications for diagnosis and management. Although SCAD typically only affects one coronary artery, MV dissections are reported in approximately 9% to 23% of cases.5,58,62,64,68,74,76,112 In a 2014 study conducted by Saw et al., 81% of patients presented with a single isolated coronary artery dissection, while 19% experienced multivessel involvement.74 Within this group, 9.5% 59 had dissection in more than one noncontiguous coronary artery.74 Nakashima et al. documented that 11% of their patients experienced dissection in at least two vessels while Tweet et al. noted MV dissections in 23% of their patients, with 16% involving two vessels and 6% involving three.62,68 Interestingly, they also observed simultaneous LMCA, mid LAD, OM, and RCA dissections in one postpartum patient.68 Patients with MV SCAD may experience a worse prognosis than those with SV SCAD, possibly due to a higher ischemic burden, larger myocardial infarctions, severe left ventricular systolic dysfunction, and elevated risks of arrhythmogenicity and heart failure.112 However, very few studies have directly compared patients with MV and SV SCAD.112 In a recent study (2023) by Salamanca et al., MV SCAD patients were found to have a higher prevalence of NSTEMI presentations (73% versus 52%), hypothyroidism (22% versus 11%), and anxiety disorders (32% versus 16%).94,112 While not statistically significant, patients with MV SCAD were also more likely to have hypertension and extracoronary vascular abnormalities than those with SV dissections.112 Furthermore, left main, LAD, and multivessel involvement is often more prevalent among patients with P-SCAD.15,49,70 Consequently, there is a higher incidence of a reduced EF, as well as more life-threatening complications.70 Both Tweet and Chen noted significantly more proximal and multivessel involvement in P-SCAD patients, as well as a greater prevalence of reduced EF at presentation.66,69 These findings suggest that the combination coronary distribution and peripartum status may contribute to a more severe clinical profile, underscoring the need for further research and clinical attention in this specific subset of SCAD cases. 60 Diagnosis Early and accurate diagnosis of SCAD is crucial as SCAD management differs significantly from that of atherosclerotic ACS, both in the cardiac catheterization laboratory and afterward.5,85 Diagnosing SCAD is a complex process that involves multiple tests and requires perceptive clinical judgment to differentiate it from other conditions.17 This is especially true during pregnancy and postpartum, where SCAD presents unique challenges.17 Therefore, it is essential to have a comprehensive diagnostic strategy for effective management and to address the specific challenges that patients in these populations face.8,17,113 Early Diagnostic Methods Clinical suspicion for SCAD is often prompted by patient characteristics, particularly demographics such as young age, female gender, and the presence of few or no traditional cardiovascular risk factors.5 SCAD has also been associated with specific genetic disorders such as vascular EDS, LDS, and APKD.85 In patients with ACS who have a personal or family history of any of these disorders or exhibit suggestive clinical features, the possibility of a SCAD diagnosis should be considered.85 While symptoms of SCAD may resemble those of other ACS causes and are not a reliable diagnostic marker, potential triggers, such as intense emotional or physical stress, have been reported some cases.85 If symptom onset is evident during specific activities, such as isometric exercise, it may increase clinical suspicion of SCAD.85 However, these symptoms can also be related to other causes of ACS, such as emotional stress in Takotsubo syndrome or physical exertion leading to the rupture of atherosclerotic plaque.85 Therefore, these 61 factors alone cannot confirm or rule out SCAD, but they can help healthcare providers determine the likelihood of SCAD as the primary diagnosis.85 Various characteristics influence the pretest probability of SCAD prior to preforming a cardiac catheterization.85 Almost all patients with SCAD present with symptoms of ACS, as well as ECG findings consistent with ischemia and evidence of wall motion abnormalities.5,85 When a patient presents with chest pain, a 12-lead electrocardiogram (ECG) is the first essential diagnostic step, ideally conducted within 10 minutes or immediately upon admission.17 ECG changes, such as ST-elevations and Twave alterations, indicate STEMI and may require immediate angiographic assessment for further diagnosis and management.1,17,114 These ECG alterations suggest the affected artery and indicate the severity of myocardial ischemia.17 In patients with SCAD, STEMI is observed in 75-80% of cases.17 However, SCAD can also manifest in other ECG patterns, including bigeminy, absence of ST-segment or T-wave changes, or diffuse STsegment depression.17 While there are no diagnostic biomarkers specific to SCAD, elevated levels of troponin, as well as creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and atrial natriuretic peptides (ANP) are linked to ACS and can potentially serve as indicators for early SCAD diagnosis.17,85 The majority of SCAD patients present with elevated levels of troponin; however in some cases, patients may initially present with normal cardiac enzyme levels, especially if their presentation in either early or delayed.5,85 In these cases, it is important to conduct serial monitoring of high-sensitivity troponin levels, as they can significantly increase within a matter of hours.5,85 For instance, a case study by Jofré et al. demonstrated this pattern: a patient's troponin level initially recorded 62 at 0.45 ng/mL escalated to over 50 ng/mL, while their CK level rose from an initial 72 U/L to 3800 U/L, and CK-mb from 2.8 U/L to over 300 U/L.17 Patients presenting with borderline troponin elevation and nonspecific ECG findings may introduce uncertainty in the diagnosis of SCAD.115 In these cases, alternative imaging techniques such as coronary computed tomography angiography (CTA), echocardiography, myocardial perfusion imaging (MPI) or cardiac magnetic resonance (CMR) can be used for further evaluation.115 These tests can help reveal the presence of myocardial ischemia or infarction, which may then prompt a coronary angiogram for a more precise diagnosis.115 Diagnostic markers may include identifying regional wall motion abnormalities through echocardiography, observing diminished myocardial perfusion on coronary CTA, or detecting regional endocardial or late gadolinium enhancement on CMR.115 Coronary Angiography and SCAD Lesion Classifications A timely and accurate diagnosis is crucial for effective treatment of SCAD, as misdiagnosis can lead to the administration of unnecessary and potentially harmful treatments designed for atherosclerotic disease.8 A low pretest probability for coronary artery disease may indicate a non-coronary diagnosis and delay an invasive diagnostic approach, especially in NSTEMI patients.116 However, invasive coronary angiography remains the gold standard for diagnosing SCAD and should be always performed within recommended timeframes following the diagnosis of ACS.116 The typical angiographic appearance of SCAD is characterized by contrast staining of the arterial wall and multiple radiolucent lumens, as well as possible spiral dissection or intraluminal filling defects.5,117 However, this “pathognomonic” appearance 63 is only present in less than 30% of cases, which can make diagnosing SCAD particularly challenging.5,74,117,118 Additionally, limited familiarity with nonpathognomonic angiographic variants among angiographers significantly contributes to the underdiagnosis of SCAD.117 Therefore, it is crucial for clinicians to become more familiar with the various angiographic presentations of SCAD to ensure correct diagnosis.116,117 In 2015, Yip and Saw proposed a classification system to assist with the diagnosis of SCAD during invasive coronary angiography.85 This approach categorizes the condition into three types based on the lesion’s type, length, and degree of stenosis.48,85,101 Type 1 describes the pathognomonic appearance of SCAD.114 It is characterized by a intimal tear, which allows the contrast to pass through the false lumen and stain the arterial wall, revealing multiple translucent lumens indicative of the formation of a false channel within the artery.48,85,119 These lesions can be more challenging to treat, but are associated with a lower risk of clinical progression (when managed conservatively), and fewer complications during PCI.48,85 Type 2 SCAD is the result of an IMH, characterized by a long, smooth narrowing, often exceeding 20 mm, and demonstrates varying degrees of severity.3,40,114 It can manifest as a diffuse stenosis with normal artery segments at the proximal and distal ends (type 2A) or it can extend to the distal tip of the vessel (type 2B).5,101,114,120 While this is the most common type of SCAD, accounting for up to two-thirds of dissections, its angiographic appearance is not widely recognized and is frequently overlooked or misinterpreted.40,48 For angiographers who are not familiar with this pattern or when lesions are shorter than 20 to 30 mm, intracoronary imaging may be necessary to confirm SCAD diagnosis.40 64 Type 3 is the least common form of SCAD.48 It is characterized by the appearance of single or multiple focal stenoses, typically less than 22 mm in length, and closely resembles atherosclerotic plaque making it the most difficult to diagnose.40,121 Angiographic features such as a lack atherosclerotic plaque, haziness, increased tortuosity, longer lesions (11-20 mm), and linear stenosis can be helpful to differentiate type 3 SCAD from atherosclerosis.40,48 Additionally, Intravascular imaging techniques like IVUS or OCT are required to confirm the presence of IMH and diagnose SCAD.5 The angiographic appearances of SCAD have been reported at various rates; however, type 2 SCAD consistently emerges as the most prevalent subtype across studies. In 2014, Saw et al. reported the occurrence of type 1 SCAD in 29.1% of patients, type 2 in 67%, and type 3 in 3.9%.74 These findings were consistent with their subsequent analysis of 1002 dissected arteries, where type 1, 2, and 3 SCAD were observed in 29%, 60%, and 10.8% of the analyzed arteries, respectively.56 Jackson et al. reported similar rates, with 24.2% of SCAD cases identified as type 1 and 9.1% as type 3.109 In contrast, Nakashima et al. reported a higher incidence of type 1 SCAD (43%) and a lower incidence of type 3 SCAD (2%).62 Similarly, Sharma et al. observed that 34% of their 113 patients had type 1 SCAD, while only 1% had type 3 SCAD.15 They also reported a high prevalence of type 2 SCAD, which accounted for 75% of their cases. Furthermore, Jackson et al. documented 2A as the most prevalent variant of type 2 SCAD, at 43.9%, while 2B was observed in only 15.2% of cases.109 The Yip-Saw classification, while valuable, has limitations in accurately categorizing atypical forms of SCAD, such as extensive, proximal dissections, diffuse nonfocal narrowings, and hybrid lesions.85 As a result, other authors have proposed to 65 expand this classification by including a fourth type of SCAD, which would addresses diagnostic challenges posed by vessel occlusions that do not fit into the initial three categories.85,101 Type 4 SCAD is described as a total occlusion that resembles thromboembolic disease, most often affecting distal vessel segments.2,46,101 Diagnosing SCAD becomes particularly difficult in this context as it requires specific SCAD indicators immediately after restoring blood flow of during PCI, or after confirming normal distal flow and ruling out potential causes of coronary embolism at follow-up.101 Type 4 SCAD has been reported in literature but is not commonly used in clinical practice.2 Jackson et al. found that type 4 SCAD accounted for 7.6% of their cases, which shows that it is present but less common than other SCAD types.109 However, a more recent observational study by Mori et al. involving 302 patients revealed a significantly higher prevalence of type 4 SCAD, with 26.8% of patients having this subtype.122 The study also highlighted a strong association between type 4 SCAD and STEMI presentation, with 71.6% of STEMI patients having type 4 SCAD compared to only 39.3% with other SCAD types.122 This suggests that Type 4 SCAD may have a distinct clinical presentation and could be more prone to severe complications.122 While angiographic classification aids in recognizing SCAD as an entity, it does not guide therapeutic decisions or impact outcomes.121 However, classifying SCAD based on the presence or absence of intramural hematoma (IMH) and additional intimal dissections, as well as specific length/stenosis parameters provides valuable insights into a patient's susceptibility for early and severe SCAD extension.121 A retrospective investigation involving 240 SCAD patients conducted by Waterbury et al. revealed that the angiographic identification of isolated IMH was linked to an increased risk of early 66 clinically significant SCAD extension in conservatively treated patients.121 Factors such as lesion length and stenosis severity were identified as additional parameters contributing to an increased risk of acute extension.121 Important Considerations A crucial aspect in the differential diagnosis of SCAD involves distinguishing between non-atherosclerotic SCAD (NA-SCAD) and a dissection resulting from atherosclerotic plaque rupture or induced by catheters.114 When an atherosclerotic plaque ruptures, contrast penetration into the plaque core may appear as a false lumen, mimicking a type 1 lesion.85 This may even progress into a localized plaque dissection; however, when observed, these characteristics are typically limited to the plaque's location.85 A plaque rupture can also result in the formation of coronary thrombus.85 When this thrombus recanalizes, it can produce multiple channels, resembling type 1 SCAD on angiography.85 Additionally, long atherosclerotic lesions may mimic the classic type 2 appearance, especially when located in the mid to distal artery segments.85 In situations of diagnostic uncertainty, several factors can provide valuable insights to differentiate between SCAD and atherosclerosis. For instance, patients with NA-SCAD lack atheroma and possess more fragile arterial walls, making it difficult to limit the expansion of the dissection.114 As a result, these patients frequently exhibit more extensive dissections, while unaffected segments appear to be smooth on angiography.114 Additionally, the IMH in SCAD is frequently constrained by arterial branch points which serve as barriers to axial extension, while atherosclerotic plaque tends to cluster at vessel bifurcations.85 Luminal thrombus, although not a typical feature of SCAD, can also provide valuable information for differential diagnosis.85 In cases of occlusive SCAD or 67 when fenestrations connect true and false lumens, luminal thrombus may be present.85 However, if significant thrombus or downstream embolization is observed, alternative diagnoses should be considered.85 Furthermore, coronary vasospasm may appear as a long, smooth stenosis, similar to a type 2 SCAD lesion.85 Administration of intracoronary nitrates can help ease the spasm and improve diagnostic clarity, but caution is required as vasospasm is also associated with SCAD.85 When diagnosing SCAD it is also crucial to consider its potential overlap in clinical presentation with Takotsubo cardiomyopathy (TTC). Intravascular imaging plays a pivotal role in differentiating between these two conditions, especially when SCAD affects the LAD, leading to septal and apical wall motion abnormalities that resemble those seen in TTC.115 This resemblance can pose challenges in diagnosis, particularly when there is no overt dissection plane visible on angiography.115 Both SCAD and TTC predominantly impact women and are associated with hormonal changes and stress, often manifesting as angina and ACS.85,101 However, TTC tends to affect an older patient population compared to SCAD.115 Additionally, diagnostic criteria for TTC necessitates the absence of images consistent with acute plaque rupture, whereas SCAD is characterized by clear angiographic abnormalities resembling atherosclerosis.123 TTC also exhibits regional wall motion abnormalities beyond a single epicardial vascular distribution, setting it apart from the more localized impact of SCAD.123 A comprehensive evaluation, incorporating angiography and intravascular imaging, is vital for accurate and timely differentiation between these non-atherosclerotic causes of myocardial infarction. 68 Other Angiographic Findings Additional angiographic features associated with SCAD include increased coronary tortuosity and a predilection for more distal coronary segments (in contrast to atherosclerotic disease).124 In a study by Sharma et al., the prevalence and severity of coronary tortuosity were assessed using a simplified definition.15 The condition is characterized by excessive twisting or curving of the coronary arteries.15 Their criteria defined tortuosity as at least one change in vessel direction by 90 degrees or more.15 The study classified the condition into two groups: mild tortuosity, which affected only one major coronary artery or two branch vessels, and severe tortuosity, which affected more than one major coronary artery.15 The study found that coronary tortuosity is quite common among patients, with 12 patients (11%) showing no tortuosity, 32 patients (30%) having mild tortuosity, and 63 patients (59%) exhibiting severe tortuosity.15 Symmetry signs such as intravessel (symmetrical angles occurring within a single blood vessel), multivessel (symmetry is observed across multiple blood vessels), and the corkscrew sign (a helical or spiral shape) are also markers of tortuosity. Among patients with extracoronary vasculopathy, these signs were significantly more prevalent, indicating a possible association with broader vascular abnormalities.79 Furthermore, FMD was linked to a higher tortuosity score and a greater prevalence of the angiographic corkscrew sign and multivessel symmetry sign.79,125 The discovery of FMD, or other related artery conditions, can often help confirm a diagnosis of SCAD. This is particularly true when other potential causes, such as atherosclerosis, have been ruled out through thorough catheter-based angiography, currently the only validated method.3,125 69 Kim et al. provided a detailed analysis of FMD and SCAD, focusing on their angiographic features.38 According to their findings, FMD is mainly characterized by the appearance of a "string of beads" in angiography, which is observed in over 70% of adult patients, especially women.38,85 This attribute is an indication that multiple arteries are affected by the disease, although the "beading" pattern is different from that of noncoronary FMD and may indicate another type of arterial dissection.125 Advanced Imaging Techniques In cases of ambiguous angiographic findings, the use of IVUS and OCT techniques can provide clarity and greatly enhance diagnostic accuracy.116 These techniques are typically reserved for type 3 and some type 2 lesions, as well as for guiding and optimizing PCI outcomes, due to the increased arterial fragility in SCAD.116 Despite potential concerns of iatrogenic injury, accurate diagnosis is crucial for determining the appropriate patient management strategies for atherosclerotic and SCADassociated ACS.116 This includes determining whether immediate PCI or a conservative approach is warranted, as well as planning the appropriate medical treatment and followup.116 OCT is the preferred imaging technique for SCAD lesions. High-resolution images, ranging from 10 to 20 μm, of the coronary vessel wall can be obtained and provide more detailed visualization of the true (TL) and false (FL) lumens, accurately identifying intimal-medial flaps.3,42,85,101,109,114 Key characteristics, including the FL’s crescent-shaped appearance, the presence of a "fenestration" or channel between the TL and FL, and abnormal features of the undissected coronary segments has been observed in several case reports and small series.109 Distinguishing this communication is vital as it 70 helps in more fully understanding the extent and type of the dissection within the artery.42,85,114 To highlight the importance of OCT, Jackson et al. conducted a thorough examination of imaging data from 68 dissected vessels.109 This included a detailed analysis of SCAD's characteristics, enabling the identification of crucial diagnostic features such as the structural impact of SCAD in both fenestrated and non-fenestrated lesions.109 Among the fenestrated cases, 25 exhibited clear communication between the True Lumen (TL) and False Lumen (FL), with 11 displaying localized fenestration and 6 featuring multiple fenestrations.109 Non-fenestrated cases, on the other hand, exhibited a more prominent normalized external elastic lamina (EEL) area, particularly in the proximal dissected area (9.1% compared to -1.9%) and at the point of maximal stenosis (-3.8% compared to -27.7%), suggesting significant arterial damage or remodeling in these lesions.109 Notably, the dissected segments showed a considerable increase in intima-media thickness compared to normal segments, with non-fenestrated cases displaying a significantly smaller intimamedia area.109 Furthermore, non-fenestrated dissections were associated with higher rates of STEMI presentations (46.5%) compared to fenestrated dissections (24%), suggesting an association with more severe clinical manifestations.109 However, luminal thrombus was more prevalent in fenestrated lesions (36%) than in non-fenestrated lesions (14%).109 While angiographic analysis did not reveal significant differences in lesion length, OCT visualization showed significantly longer dissections.109 Specifically, fenestrated lesions had a mean lesion length of 44.13 mm, compared to 28.1 mm in non-fenestrated 71 lesions.109 In contrast, angiography estimated these lengths at 54.7 mm and 59.3 mm, respectively.109 These findings underscore the enhanced precision of OCT in delineating the structural characteristics of SCAD, offering valuable insights beyond conventional angiographic assessments.109 IVUS also serves as an effective diagnostic tool for SCAD, offering improved vessel wall penetration to capture the full depth of the IMH.115,116 This technique effectively differentiates atherosclerotic plaques from SCAD by providing clear visualization of the true and false lumens, as well as the severity of false lumen thrombosis.114 Despite its ability to provide a comprehensive view of the vessel wall and EEL, IVUS has poor spatial resolution which limits its ability in detecting finer details, such as the intimal-medial membrane.114 This can lead to diagnostic uncertainty and potentially impact the accuracy of the diagnosis.114,115 In their 2020 study, Ciurica et al. evaluated the effectiveness of IVUS in identifying critical characteristics of SCAD.126 They analyzed IVUS images from 15 SCAD cases encountered during routine clinical procedures, and identified various features, including the TL and FL, the extent and contents of the FL, the intima-media membrane, the EEL, the underlying adventitia, and the presence of fenestrations.126 The study revealed that the FL was completely evident in 87% of cases, and the EEL was visible in 80%.126 Moreover, a circumferential dissection was observed in 20% of cases.126 In all instances, the FL content exhibited lower echogenicity than the surrounding tissues, and no fenestrations were observed.126 These findings suggest that, despite having lower resolution, IVUS remains a valuable tool for visualizing the crucial features of SCAD, primarily due to its deep penetration.126 72 Non-Invasive Imaging Conventional approaches such as coronary angiography typically serve as the initial diagnostic step for SCAD. However, there are situations where these methods may fall short in providing definitive results or when the inherent risks of invasive procedures are elevated.3,20,42,49 In such scenarios, the need for additional diagnostic tools becomes essential.42 Some non-invasive modalities that offer supplementary insights include Coronary Computed Tomography Angiography (CCTA), Cardiac Magnetic Resonance Imaging (CMR), and nuclear myocardial perfusion imaging.20 CCTA has been utilized both in the initial diagnosis of SCAD and to assess healing; however, CCTA diagnostic criteria for SCAD need further refinement.3 Several case series and individual case reports have demonstrated the efficacy of CCTA in the identification of acute SCAD.2 CCTA findings in SCAD reveal distinct characteristics, including the absence of atherosclerotic plaque, tapered luminal stenosis, abrupt luminal stenosis marked by a sharp contrast demarcation, luminal occlusion, intramural hematoma with hemorrhage, dissection flap, and perivascular epicardial fat stranding.2 Additionally, CCTA can help differentiate between atherosclerosis and SCAD, especially during recovery.85 The presence of coronary calcification or positive remodeling of lipidemic plaque on CTCA can provide support for a diagnosis of atherosclerosis.85 In contrast, complete recovery with no persistent vessel wall abnormalities is indicative of SCAD.85 However, the spatial resolution limitations of CCTA can pose challenges in identifying SCAD lesions, particularly in distal segments.101 These lesions might not always lead to significant lumen stenosis, and achieving contrast penetration into the 73 false lumen may be challenging.101 Additionally, Type 3 SCAD, which can resemble short-segment narrowing similar to atherosclerotic plaques, may not be easily discernible on CCTA.3,42,48,49,114 Similarly, the abrupt narrowing characteristic of Type 2 SCAD, can also be easily overlooked.42,101 Eleid et al. documented three cases in which SCAD was not initially identified on CCTA, but was later confirmed using coronary angiography.101,127 They also provided retrospective CCTA findings in patients during the acute phase of SCAD, with the most prevalent observations being abrupt luminal narrowing and IMH, resembling noncalcified atherosclerotic plaque on CCTA.101,127 Similarly, in 2019, Tweet et al. reported that initial cCTA only detected SCAD in 25% of patients, while subsequent coronary angiography confirmed the diagnosis in over half of the patients.128 However, the same study by Tweet et al. exhibited key SCAD-related features on CCTA, including sudden or gradual artery narrowing and vessel wall thickening suggestive of IMH.42,128 IMH was observed as discrete vessel wall thickening in 50% of patients, and abrupt luminal stenosis was the most common finding in 64% of patients.128 Moreover, while all patients experienced ACS, myocardial hypoperfusion was evident in only half, and none showed coronary calcification.42,128 Additional features such as epicardial fat stranding and coronary tortuosity were also noted, facilitating the diagnosis of SCAD.42,128 Furthermore, CCTA could serve as a beneficial tool for the noninvasive monitoring of SCAD patients, especially those with dissections occurring in proximal or large-caliber coronary arteries.3 A study by Roura et al. showed that 83% of patients exhibited healed dissections withing 3-6 months, demonstrating its value as a complication-free, noninvasive follow-up examination.3,42,129 Similarly, various other 74 authors have also documented that CCTA effectively visualizes coronary artery structures, identifies dissection flaps and IMH, and is valuable in monitoring the healing process after SCAD.3,49 However, when SCAD involves distal coronary arteries, side branches, or vessels with a caliber less than 2.5 mm, these areas are generally not well visualized on CCTA.3 As a result, the utility of this method is limited in many SCAD cases.3 CMR is a commonly used method for detecting and characterizing infarcts as well as identifying negative effects such as ventricular thrombus, pericarditis, and ventricular impairment.49,114,130 It is also increasingly being chosen as a diagnostic tool for SCAD.49,114,130 By detecting specific changes in cardiac tissue, such as microvascular obstruction and IMH, CMR provides an effective means of visualizing myocardial damage and assessing SCAD's impact.42,49,114 Another notable advantage of CMR is its capacity to distinguish between various conditions, including Takotsubo cardiomyopathy, myocarditis, Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA), and SCAD, by revealing delayed contrast enhancement in affected areas associated with each condition.3,42,114 Tan et al.'s study highlighted CMR's role in diagnosing and evaluating the adverse effects of acute SCAD. Their research focused on CMR indicators like LVEF, wall motion score index (WMSI), microvascular obstruction (MVO), perfusion defects, and myocardial delayed enhancement (MDE) in patients within eight days of SCAD onset.130 Results showed mean LVEF of 56.1%, mean WMSI of 1.27, and 15 patients with SCADrelated MDE, which was consistent with MI and identified through coronary angiography.130 CMR revealed FMD and vascular abnormalities in 14 patients.130 75 Among two patients undergoing pre-angiography CMR, one had subendocardial infarction, prompting further angiographic evaluation.130 The other, despite having experienced a cardiac arrest, patient exhibited normal CMR results.130 To evaluate the extent of myocardial infarction, the remaining 16 patients received CMR after their coronary angiography.130 In this group, 83% had MDE consistent with angiographic findings, and 78% had WMSI greater than 1.0.130 These findings reveal CMR's capability to detect myocardial damage and vascular abnormalities.130 However, its inability to predict future SCAD events indicates the need for further research into its prognostic role.130 While, CMR can provide valuable diagnostic and prognostic information, a normal CMR does not inevitably rule out the possibility of SCAD.3 SCAD confirmed angiographically SCAD may not have signs of infarction on MRI, which emphasizes the need for a comprehensive diagnostic approach in SCAD cases.3,49,114 However, despite its limitations in directly visualizing coronary arteries, CMR still plays a crucial role in the multidimensional assessment and management of SCAD.42 Nuclear myocardial perfusion imaging, including single-photon emission computed tomography (SPECT) and positron emission tomography (PET) scans, is valuable for assessing myocardial blood flow in rest and stress conditions.42 Although not typically the primary choice for acute SCAD cases, it is beneficial for patients presenting with ambiguous or inconsistent chest pain.42 Abnormal results may prompt further investigation with more detailed procedures, such as invasive angiography or CCTA, aiding in the potential confirmation of a SCAD diagnosis.42 76 Specific perfusion patterns can indicate SCAD-related complications in SPECT or PET imaging.42 For instance, a consistent defect in blood flow across both resting and stressed states might suggest a myocardial infarction caused by SCAD, while abnormalities appearing only during stress could signify ischemia.42 Understanding the severity and reversibility of these defects is critical in evaluating SCAD's impact and predicting patient recovery.42 Furthermore, myocardial flow reserve measured in cardiac PET imaging offers critical prognostic insights.42 This technique is also employed to assess the viability of cardiac tissue post-injury.42 For individuals with a history of SCAD, PET imaging can be essential in determining whether new episodes of chest pain are due to ongoing ischemia.42 Vadi et al. discuss the important role of SPECT and Myocardial Perfusion Imaging (MPI) in identifying and treating SCAD.131 It has demonstrated effectiveness in evaluating the myocardium's sustainability and revealed perfusion defects potentially related to coexisting CAD in territories separate from SCAD.131 Critical insights for treatment planning and long-term follow-up can support determining the most appropriate therapeutic approach.131 Treatment / Management Options The approach to managing SCAD is controversial and presents significant therapeutic challenges due to the limited evidence available to guide clinical decisions.114 The absence of randomized controlled trials (RCT’s) comparing medical therapies and revascularization strategies for SCAD complicates the determination of optimal management.114 Consequently, treatment strategies rely heavily on expert opinions.114 77 Management approaches should be individualized, based on various clinical factors such as presentation, hemodynamic stability, dissection size and site, affected vessel flow, and the number of involved vessels.17,132 A crucial aspect of SCAD management involves a multidisciplinary team, including cardiologists, intensivists, and gynecologists, working collaboratively to achieve rapid stabilization and continuous hemodynamic monitoring.17 The success of treatment directly hinges on timely diagnosis and the individualization of treatment strategy.17 Conservative/Medical Management During the acute phase, the primary treatment goal is to restore or preserve myocardial perfusion and cardiac function.3 Treatment options typically include conservative medical therapy, percutaneous coronary intervention (PCI), or coronary artery bypass surgery. While RCTs investigating SCAD management strategies are lacking, an emerging body of evidence from cohort studies published between 2012 and 2022 suggests that adopting a conservative management may be the preferred approach for SCAD, particularly in patients that are clinically stable with low risk anatomy, favorable distal coronary flow (TIMI score: 2-3), and no evidence of ongoing chest pain or ischemia.132–134 Furthermore, observational data suggests that 70% to 97% of patients selectively restudied weeks to months after conservative management display angiographic "healing" of SCAD lesions.5 In a minority of patients, persistent dissection is observed; however, the reason for this is unclear, and it is unknown if subsequent very late healing may have occurred in these cases.5 A study evaluating 131 SCAD lesions found that 88.5% of cases experienced spontaneous healing, except for those where repeat angiography was performed early, within 35 days from the initial event.5 Notably, 78 all cases with repeat angiography after 35 days showed complete angiographic healing, suggesting a time-dependent factor in SCAD's healing process.5 A 2023 retrospective cohort study conducted by Feldbaum et al., illustrates a significant shift in the management strategies for SCAD over the years, highlighting predominant trend towards conservative approaches.134 Notably, between 2013 and 2019, there was a substantial rise in the adoption of conservative management from 35% to 89%.134 Furthermore, the rates of revascularization, encompassing both CABG and PCI, exhibited a decreasing trend over the same timeframe.134 These observations may be indicative of the growing body of evidence supporting the natural healing of arteries postSCAD, favorable clinical outcomes associated with conservative approaches, and a heightened risk of complications in patients undergoing PCI.134 Additionally, the increasing awareness of SCAD likely contributes to the identification of less severe cases that do not necessitate intervention, thereby contributing to the observed decline in revascularization rates over time.134 Consistent with these findings, a recent prospective observational series of 750 SCAD patients, researchers discovered that a 84.3% of the cases were resolved without the need for surgical intervention.3,56 This suggests that specialized centers can effectively manage the majority of SCAD cases through conservative approaches.3 Previously, the standard treatment approach for acute SCAD was similar to the treatment of ACS caused by atherosclerotic disease.101 Fibrinolytics were initially used to treat STEMI and were considered appropriate, even in the context of SCAD.17 However, thrombolytic therapy no longer recommended due to the increased risk of clinical deterioration caused by the extension of dissection and IMH.17,40,43 A retrospective 79 review by Shamloo et al. drew attention to the dangers associated with thrombolysis in SCAD.40,43 Out of 87 patients who underwent thrombolytic treatment, 60% experienced worsening conditions, necessitating rescue procedures like PCI or CABG.40,43 Heparin, also commonly administered in ACS, lacks proven benefits for SCAD management.43 While it may resolve overlying thrombus and improve true lumen patency, anticoagulation can also prolong dissection.40,43 The European Society of CardiologyAcute Cardiovascular Care Association advises against using thrombolytic therapy when SCAD is suspected and recommends that anticoagulants, such as heparin, be discontinued once SCAD diagnosis is confirmed unless there are other indications for their continued use.101 However, in remote centers where transfer protocols for primary PCI are unavailable, thrombolysis should not be withheld for STEMI patients, given the higher prevalence of thrombotic occlusions compared to SCAD.40 Several studies have advocated for the administration of antiplatelets, betablockers, nitrates, and angiotensin-converting enzyme (ACE) inhibitors in the treatment of SCAD patients.17 However, determining the most effective medication regimen is challenging due to a lack of conclusive evidence from comparative research.17,135 Nitrates are often used in the initial treatment of SCAD, as their vasodilatory effects can help alleviate ischemic symptoms caused by vasospasm during the acute phase of SCAD.40 While they may be beneficial in the short term, nitrates are generally not considered a standard option for long-term management of SCAD.40 Currently, aspirin stands as the most widely employed drug in SCAD treatment, chosen for its minimal side effects and established effectiveness in managing ACS and providing secondary prevention of CAD.13,17,40,43 Patients who receive stents are recommended to undergo dual antiplatelet 80 therapy (DAPT) with aspirin and clopidogrel for a duration of 12 months, followed by lifelong monotherapy with aspirin.114 Clopidogrel is generally preferred over other potent P2Y12 inhibitors like ticagrelor and prasugrel, as they are associated with a higher bleeding risk which could exacerbate the dissection.13,40 However, the efficacy of clopidogrel in treating SCAD patients who have not undergone stenting is uncertain. In the acute phase, it may appropriate to use dual antiplatelet therapy (DAPT) with aspirin and clopidogrel, regardless of the treatment strategy, due to the frequent presence of a luminal thrombus in the dissected coronary artery.101 DAPT effectively reduces thrombus formation in the false lumen caused by SCAD.13,17,101 DAPT also helps maintain the caliber of the true lumen by alleviating the compression on the true lumen and reducing the thrombus burden in the false lumen.13,17,101 Research supports this approach, including one study that identified thrombus in the in a small number of SCAD cases.101,109 However, the significance of this small amount of thrombus in causing SCAD-related ischemia is unclear, with some experts suggesting that it plays a minor role.101 According to Krittanawong et al., SCAD patients with an elevated risk of bleeding, a short-term DAPT course of 2 to 4 weeks followed by low-dose aspirin alone is considered reasonable.121 Long-term DAPT may be necessary in cases of severe lateacquired stent mal-apposition observed during follow-up.121 The duration of DAPT therapy in SCAD is subject to factors such as the lesion's location, revascularization method, and the number and size of stents used.121 Despite the theoretical risk of bleeding or dissection extension associated with antiplatelet therapy, including low-dose aspirin 81 monotherapy, particularly in patients with IMH, the consensus leans towards lifelong low-dose aspirin and one year of DAPT following ACS guideline-based therapy.121 Beta-blockers are crucial in treating SCAD, with their efficacy inferred from the benefits they provide in treating acute aortic dissection and atherosclerotic ACS.13,40,101 Beta-blockers have been shown to effectively reduce arterial shear stress and ventricular arrhythmias, leading to improved long-term survival.13,43 Studies have indicated that SCAD survivors have a lower risk of recurrence when undergoing beta-blocker therapy, which has resulted in the recommendation of extended use of beta-blockers in postSCAD management.13,40,101 While beta-blockers are typically administered both during the acute phase and as part of long-term treatment following SCAD, the specific effectiveness of beta-blockers for SCAD treatment has yet to be comprehensively studied.13 Statins are widely recognized for their lipid-lowering benefits in atherosclerotic coronary artery disease and post-MI care.13,43 However, cholesterol accumulation is not typically associated with SCAD, making the effectiveness of statins uncertain in patients with a normal lipidemic profile.13,43,101,114 Additionally, retrospective data, including a Mayo Clinic study, shows a slight increase in the risk of recurrence among SCAD patients who use statins.13,43,101 Therefore, statins should only be prescribed to SCAD patients with existing dyslipidemia.13,40,43,101 Furthermore, additional medical treatments aimed at lowering arterial pressure and protecting the myocardium, such as angiotensin-converting enzyme (ACE) inhibitors, are also recommended in the context of SCAD.114 While ACE inhibitors are not typically the first-line treatment for SCAD, they are advised for individuals who 82 experience a significant decrease in their LVEF following ACS significantly if the ejection fraction drops to 40% or lower.13,17,40 Following a myocardial infarction, their use is a class IIa indicator, with a stronger class I indicator for considerable left ventricular impairment.13,40 Nevertheless, due to limited research on SCAD patients, clinicians often reserve ACE inhibitors for those with significant LV dysfunction.13 In a cohort study conducted by Feldbaum et al., the utilization of statins demonstrated a substantial increase from 47% before 2013 to 89% in 2019.134 Notably, only 45% of patients prescribed statins had documented dyslipidemia, suggesting a broader application of statins beyond conventional indications.134 Additionally, the number of patients discharge with DAPT also increased during this period, from 56% to 82%.134 In 2016, Saw et al. reported that upon discharge, 92% of patients were prescribed aspirin, 83.0% beta-blockers, and 62.2% clopidogrel.28 Moreover, 49.2% of patients were prescribed an ACE inhibitor or angiotensin receptor blocker (ARB), while 36.7% received statin therapy.28 Similar rates were reported by Chen et al. in their 2019 study, where at the time of discharge, aspirin, clopidogrel, statins, beta-blockers, and ACE inhibitors or ARB’s prescribed to 94%, 82%, 81%, 88%, and 63% of patients, respectively.133 These findings collectively reinforce the comprehensive nature of medical interventions in the management of SCAD. Revascularization While conservative management is typically favored over revascularization, instances of active ischemia, hemodynamic instability, high risk anatomy, or unsuccessful medical management may necessitate intervention through PCI or CABG.17,43,114,132,135,136 In a 2019 study, Saw et al. analyzed the occurrence of 83 revascularization procedures in 110 patients with SCAD, of which the majority were PCI.56 Among these patients, 39.1% reported ongoing chest pain, and 34.5% exhibited ischemia.56 Severe stenosis due to dissection was a significant factor, identified in 31.8% of cases.56 Additionally, proximal dissections of major coronary arteries were present in 22.7% of patients, while more extensive artery dissections exceeding 3mm in diameter were observed in 14.5%.56 Other reasons for revascularization included iatrogenic catheter-induced dissection, left main coronary artery dissection, ventricular arrhythmias, recurrent in-hospital chest pain, hemodynamic instability, multiple coronary dissections, and focal or tubular dissections, each accounting for less than 10% of cases.56 In a 2021 meta-analysis conducted by Feldbaum et al., 27.8% and 7.8% of patients presenting with STEMI and UA/NSTEMI , respectively, were treated with revascularization.106 Revascularization was also more commonly employed in cases of type 1 SCAD that included the left main trunk (LMT) or LAD artery and TIMI 0 flow at baseline.106 The prevalence of TIMI 0 or 1 flow at baseline and the occurrence of lethal arrhythmias in SCAD-STEMI patients likely contributed to the higher utilization of PCI and CABG in this group.106 Furthermore, in a retrospective cohort study conducted in 2023, revascularization techniques were more common in young patients, those with P-SCAD, and cases of LM, LAD, and multivessel dissections.134 These findings align with previous studies, which indicate more severe manifestations and higher likelihood of revascularization in peripartum patients and those with high-risk lesions in the LM or proximal LAD.134 84 Percutaneous Coronary Intervention The incidence of PCI in SCAD patients varies significantly across different studies, with rates ranging from 13.6% to 50.3%.106 While PCI can be a viable option, it should only be considered for lesions in patients with clinically high-risk features, in order to balance the need for intervention against the potential complications.137 PCI can effectively reopen the true lumen, alleviate ischemia, and seal the dissection; however, in SCAD-affected arteries, PCI is complex and less predictable, with higher rates of complications and failure, even when maintaining distal coronary perfusion.3,17,43,132,136,137 This is largely influenced by the increased susceptibility to iatrogenic reactions during catheter manipulation, angioplasty, or stenting observed patients with SCAD.17 Recent studies report that only approximately half of PCI attempts in cases of SCAD are successful, and there is a significant risk of iatrogenically induced extension of the dissection.138 Additionally, up to one-third of PCI cases are complicated by hematoma propagation, which often necessitates the use of multiple unplanned stents.3 The subsequent resorption of the hematoma may result in late strut malapposition, further complicating the revascularization process.3 A PCI procedure is considered technically successful when dilation improves the baseline Thrombolysis in Myocardial Infarction (TIMI) grade from 0 to 1 or maintenance/improvement in TIMI grade from 2 to 3 flow.68 In acute clinical scenarios, the primary focus is on optimizing coronary flow rather than merely improving lesion stenosis, as maintaining adequate blood flow is crucial for successful outcomes.68 This approach is particularly significant because the dynamics of residual vessel dissection differ fundamentally from those of the dilated segment, making coronary flow a more 85 critical marker for clinical success.68 In a study conducted by Hassan et al., PCI was performed on 75 patients with SCAD.137 Of these patients, 80% underwent PCI as their primary treatment strategy, 14.6% received PCI only after initial medical treatment failed, and 5.3% received PCI after thrombolysis.137 The success rate for PCI was 34.7%, while it was partially successful in 37.3% of cases and unsuccessful in 28.0%.137 Final TIMI 3 flow was observed in 72.0% of patients, and improved TIMI flow with PCI occurred in 62.7% of cases.137 The most effect strategy for PCI in SCAD lesions remains unclear.137 In a study by Hassan et al., 73.3% of patients who underwent PCI were treated with stents, 16% were treated with angioplasty alone, and in 10.7% of cases, wiring attempts were unsuccessful.137 In 2019, Lobo et al., reported stenting was the most common method of revascularization in STEMI patients, both with and without SCAD.139 They also noted that in cases of SCAD, the number of stents used was significantly greater than for patients with atherosclerosis.139 The selected approach should be individualized and guided by anatomical characteristics and dissection severity.137 Careful attention is required to prevent catheter-induced dissection during guidewire manipulation. Avoiding deep catheter engagement and non-coaxial positioning of the catheter tip, as well as refraining from strong contrast injections can help to minimize potential complications.5,74,114,136,140 Less conventional approaches have been proposed to reduce the risk of complications during PCI, including the use of angioplasty balloons capable of modifying plaque and depressurizing the false lumen, sequential stenting, bioresorbable stents, and longer stents to prevent stent migration or dissection propagation.17,114 Additionally, several cases have reported the use of scoring/cutting balloon angioplasty in 86 the treatment of SCAD, both as an initial intervention and when stenting was ineffective in restoring flow.132 However, there is currently insufficient evidence to substantiate the efficacy of these techniques.17 Coronary Artery Bypass Grafting CABG is typically reserved for unstable patients presenting with severe LM, proximal large-vessel, and multivessel dissections, or in cases where PCI is unfeasible, unsuccessful, or contraindicated.36,138 Managing LM dissections is challenging and necessitates urgent hemodynamic support and effective revascularization.139 Very few case reports have documented experience with PCI stent revascularization LM SCAD lesions, and LM stenting carries inherent risks, including potential dissection propagation into the LAD and circumflex coronary arteries.139 In certain instances, technical infeasibility of stenting necessitates emergent CABG.139 Difficulties in wiring into the true lumen distally may also prompt emergent CABG, as observed by Nakashima et al.62 According to Lionakis, previous reports suggest that emergency CABG is necessary in approximately 2.2% to 7.4% of patients initially treated with medical therapy or PCI.139 Similarly, Hassan et al. study reported that emergency bailout CABG was required in 5.3% of their SCAD patients treated with PCI.137 Furthermore, Lettieri et al. reported only 5 out of 134 patients required CABG due to multivessel dissection or left main coronary artery involvement.64 Among them, one patient initially underwent PCI but developed recurrent diffuse intrastent restenosis, eventually requiring CABG with an isolated left internal mammary artery-to-left anterior descending artery graft.64 Another patient, initially managed medically, developed a new dissection in a different vessel 87 after an acute coronary syndrome episode, leading to CABG and left ventricular aneurysmectomy.64 CABG generally demonstrates favorable in-hospital and short-term outcomes.17,139 In studies by Saw et al., Tweet et al., and Lettieri et al., initial CABG revascularization was employed in 0.6% to 3.7%, with a high initial success rate ranging from 87.5% to 100%.114 However, the long-term effects of CABG are not well established, as the available evidence is primarily derived from case studies, case series, or retrospective studies.17 While immediate in-hospital outcomes for CABG in SCAD cases are generally favorable, the long-term durability of the grafts is a concern.17,68,141 Reports indicate a graft survival rate of only 27%, pointing to a high late bypass graft occlusion rate.141 CABG is associated with a significant risk of bypass conduit failure, often due to increased competitive flow as the native coronary arteries heal.17,114,139 Additionally, dissected coronary artery tissues can be extremely fragile, making them less likely to hold sutures and more susceptible to anastomotic complications.114,139 Despite these concerns, successful graft anastomoses are typically achieved in all primary and nearly all secondary vessels in patients treated with CABG, including those initially managed conservatively or with PCI.114,139 Special Considerations Managing patients with P-SCAD can be challenging due to the high likelihood of large and proximal vessel dissections, which can result in extensive myocardial injury and life-threatening arrhythmias.114 Consequently, these patients often present with ACS complicated by acute heart failure or cardiogenic shock.114 In such cases, the therapeutic approach may require immediate mechanical hemodynamic support and 88 revascularization, or even cardiac transplantation.114 The beneficial effects of these therapeutic approaches have been demonstrated in case reports of pregnant women with SCAD and cardiogenic shock.114 For stable P-SCAD patients, the treatment approach mirrors that of nonpregnant patients, with additional considerations to ensure optimal outcomes for both the mother and fetus.3 While some experts recommend avoiding diagnostic coronary angiography in these patients due to concerns about fetal radiation exposure, it is important to note that maternal mortality rates are significantly high.3 With proper shielding, fetal radiation exposure can be negligible, and therefore, it is recommended to follow the standard of MI care for pregnant women.3 Furthermore, case reports suggest that CABG may be preferred over PCI in patients with P-SCAD to reduce the risk of complications such as dissection extension and aneurysm formation.114 It is crucial to approach these complex scenarios with careful consideration and individualized treatment plans. Outcomes The prognosis of SCAD is usually good, however the short- and long-term outcomes are not well established.58,64,114 Mortality rates are typically low, varying from 1 to 5% across published studies.4,114 Despite the predominant clinical presentation of in 134 SCAD patients (>90%), Lettieri et al. reported a favorable in-hospital prognosis, noting a low mortality rate of 2%.64 In a 2018 study, Krittanawong et al. also reported a fairly low in-hospital mortality rate of 4.2% in SCAD patients presenting with ACS.142 Intermediate and long-term adverse cardiovascular events are relatively common following hospital discharge.5 These complications include chest pain, depression, anxiety, and major adverse cardiac events (MACE), such as MI, recurrent SCAD, 89 revascularization, congestive heart failure, stroke, and death.5 Prior research demonstrates a high incidence of readmission at 30 days post SCAD, commonly as a result of recurrent MI.49,75 Additionally, approximately half of recurrent MI’s occur 2 days following initial discharge.49 Utilizing a Nationwide Readmissions Database from 2016 – 2017, Krittanawong et al. observed a 30-day readmission rate of 11.3%.143 More than half of readmissions were associated with cardiac events, including chest pain (24.6%), heart failure (17.5%), ACS (27.3%), and recurrent SCAD (8.3%).94 Recent reports indicate that major adverse cardiac events (MACEs) occur in 10% to 30% of SCAD cases during the 2 to 3-year follow-up period.5 Recurrent SCAD (R-SCAD) and MI is responsible for the majority of these events, accounting for 15% to 22% of cases.5 At longer term follow up, 5 to 7 years, MACE is reported in 15% to 37% of cases, predominately related to recurrent SCAD events.5 Recurrent SCAD SCAD has a high recurrence rate during both the early and late stages of the disease.37 Recurrent SCAD has been characterized as either an extension of the dissection in the proximal or distal direction, or as a de novo SCAD event, separate from the initial lesion.37,75 Extension of dissection typically occurs within 30 days from the initial SCAD event, whereas de novo R-SCAD can be observed anywhere from one month to up to 1520 years later.28,37 According to a study by Main et al., 13.9% of patients experienced recurrent SCAD, with 79% of those due to de novo SCAD and 21% caused by dissection extension.75 The median time for SCAD extension was 5 days, and R-SCAD was observed after 1487 days from the initial event.75 Recognizing the unique features and 90 pathophysiology of each event, the American Heart Association now defines R-SCAD as de novo SCAD in previously unaffected segments.75 Research indicates that R-SCAD is more prevalent in women, with proportions ranging from 74% to 100%.75 The average age of women affected by R-SCAD ranges from around 49 to 55 years, although a reported case involves an 81-year-old patient.75 In two separate retrospective cohort studies, by Tweet et al. and Clare et al., female patients accounted for all cases of recurrent SCAD.75 Additionally, in a comprehensive analysis, Chi et al. reported female predominance and an average age of 35 to 53 years across 14 cohorts, comprising a total of 4026 patients.144 Furthermore, variations in the study population, the definition of R-SCAD, and the duration of follow-up make it difficult to establish the recurrence rate of SCAD.75 Reported rates of recurrence have ranged from 9% to 27% at a median follow-up duration of 3 to 5 years.75 An Italian study showed a recurrence rate of 14% after 12 months of follow-up, while a US study reported a higher rate of 27% after a year of follow-up.75 Recurrence rates of 17% at 4-year follow-up and 29% at 10 years were reported in another US study.114 Additionally, a Canadian study found that 10.4% of patients experienced recurrent SCAD within 3.1 years.114 Treatment Related Outcomes Despite the low rates of in-hospital mortality associated with SCAD, urgent inhospital revascularization is eventually required in up to 14% of patients, most often due to extension of dissection.5 The choice of initial treatment strategy plays a crucial role in determining the outcomes of SCAD patients.5 Based on observation and retrospective studies, current recommendations favor a conservative approach as the first-line 91 management.137 Conservative therapeutic strategies, including medical therapy, have proven effective, demonstrating favorable long-term prognoses, with event-free survival rates ranging between 88% and 94% at six years.114 This is underscored by case series from the United States and Italy, reporting a 10-year survival of 92% and a 6-year survival of 94.4%, respectively.114 Approximately 5% to 10% of conservatively managed patients may experience early complications of recurrent MI as the result of extension of dissection.51 This most often occurs within the first 7 days following an acute SCAD event and requires emergency revascularization.51 In selected retrospective series with over 100 patients, inhospital revascularization was required in 2.6% to 8.5% of conservatively treated patients.5 A study by Saw et al. in 2017 further supports these findings, noting low inhospital complication rates among SCAD patients, with the majority initially managed conservatively.28 Among those treated conservatively, only 3.3% presented with dissection extension, necessitating revascularization.28 In contrast, in a systematic review of 440 SCAD patients between 1931 and 2008, Shamloo et al. found that 21% of patients treated conservatively experienced clinical progression, leading to recurrent ischemia and revascularization.143 Another large study, including 750 SCAD patients in Canada and the U.S., reported an 8.8% rate of recurrent MI, unanticipated revascularization, stroke, and repeated emergency room visits at 30 days post-discharge in conservatively treated patients.143 These findings suggest that not all SCAD patients may be suitable for conservative management, particularly those with high-risk characteristics, as this could result in subsequent hospitalizations and increased readmission rates.143 However, in cases of SCAD, PCI can be challenging and is associated with an increased risk of 92 coronary complications, failure, and suboptimal outcomes.58,114 The reported success rates of PCI vary widely, ranging from 47% to 91% according to small retrospective series.137 Notably, the success rate of PCI for SCAD is substantially lower than rates reported for atherosclerotic ACS.5,49 Case series have reported recurrent dissections and high rates of target vessel failure as significant contributing factors to MACEs in 14.6% to 47.4% of SCAD patients undergoing PCI.114 Preliminary findings from the SCAD registry at Vancouver General Hospital revealed that 6.9% of SCAD patients treated with stents required emergency surgery, 9.7% experienced iatrogenic dissection, 1.4% had stents deployed in the false lumen, and 2.8% experienced stent thrombosis.121 Urgent PCI for STEMI-related SCAD also had lower rates of achieving TIMI grade 3 flow (91% versus 98%) and exhibited a 9% failure rate as compared to atherothrombotic STEMI patients.121 Furthermore, SCAD lesions required longer and more stents, with a mean length of 62±37 mm and a range of 12–140 mm.121 Saw et al. reported unsuccessful PCI in 31.0% of SCAD cases and only partial success in 25.9%.28 Similarly, the Mayo Clinic series indicated a lower procedural success rate of 47%, with 13% requiring bailout coronary artery bypass grafting (CABG).110 In contrast, Hassan et al. observed higher success rates, with PCI procedures being successful or partially successful in 72% of cases and unsuccessful in 28%.137 They also noted higher rates of repeat revascularization in the PCI group, both in hospital and following discharge, while the Mayo Clinic series found no significant difference in the 5-year rates of target vessel revascularization and recurrent SCAD between PCI and conservative therapy groups.110,137 Lettieri et al.'s series demonstrated a 72.5% success rate for PCI and lower in-hospital major adverse cardiac events (MACE) in the 93 conservative therapy group.64 Conversely, a meta-analysis by Martins, involving 631 SCAD patients, found no significant difference in mortality, myocardial infarction, or SCAD recurrence between revascularization and conservative therapy, but highlighted a higher risk of target vessel revascularization wit PCI.137 Additionally, Hassan et al reported higher incidences of in-hospital MACE and overall major adverse cardiac events (MACE) in the PCI group, primarily driven by repeat revascularization and overall MI rates at long-term follow-up.137 Although technically feasible, CABG is not commonly used as the initial revascularization approach for SCAD.49 In fact, less than 1% of SCAD cases are referred to CABG.49 Its use is generally limited to cases with multivessel and proximal dissections, left main involvement, PCI failure, or refractory ischemia despite conservative therapy.5,49 The available literature on CABG in patients with SCAD is constrained to case reports, small case series, and retrospective observational studies with limited sample sizes.5 According to Hayes et al., CABG was used as the initial revascularization approach in 0.6% to 3.7% of SCAD patients, with initial success rates of 87.5% to 100%.5 Additionally, 2.2% to 7.4% of patients initially treated with medical therapy or PCI required emergency CABG.5 Despite high short-term technical and clinical success, CABG has low long-term graft patency due to bypass graft occlusion caused by spontaneous vessel healing and flow restoration in the native vessel.49 In a study by Tweet et al., CABG was associated with high initial technical success rates and favorable in-hospital outcomes.5,110 However, a high venous and arterial conduit failure rate was reported at the median 3.5- 94 year follow-up.110 Additionally, CABG was not found to reduce the risk of recurrent SCAD or long-term target vessel revascularization (TVR).110 While conservative therapy is the preferred option for SCAD patients, the exact treatment protocol for these individuals remains unclear.145 In the absence of specific guidelines for SCAD patients, dual antiplatelet therapy (DAPT) is often prescribed, likely influenced by its beneficial impact in patients with non-SCAD ACS.58,145 Nonetheless, aggressive antiplatelet therapy may increase the risk of IMH progression and dissection extension.145 Therefore, it is not recommended to continue heparin administration after a SCAD diagnosis has been made.145 Additionally, the role of DAPT in SCAD patients is unclear, and varies widely in clinical practice.37,145 Aspirin is recommended in the acute phase of SCAD treatment; However, there is currently no concrete evidence to support the addition of a P2Y12 inhibitor.37 In a registry study of 199 conservatively managed patients, Cerrato et al. found that the use of DAPT was independently associated with a higher incidence of adverse cardiovascular events at the 1-year follow-up compared to single antiplatelet therapy (18.9% versus 6.0%).37 The elevated risk in the DAPT group was primarily driven by an excess of MACEs during the index hospitalization (11.4% versus 1.5%).37 However, there was no notable difference in major bleeding events.37 In another study by Seidl et al., the majority of patients were treated with DAPT for 12 months, followed by aspirin monotherapy, and no major bleeding events were reported.37 Interestingly, all late recurrent SCAD events occurred while patients were on aspirin monotherapy or not on antiplatelet therapy at all.37 Furthermore, the DISCO registry found no significant difference in SCAD recurrence between dual and single antiplatelet therapy.144 95 The efficacy of common medications used to MI, including statins, angiotensinconverting enzyme inhibitors, and beta-blockers, is uncertain.145 Beta-blockers are thought to decrease arterial shear stress, which may reduce the risk of dissection extension or SCAD recurrence.144 However, beta-blocker therapy may also increase the risk of vasospasm.58 In a prospective cohort study by Saw et al., beta-blocker use was associated with a 64% reduction in SCAD recurrences over a median of 3.1 years.28,49 Chen et al. also observed a lower risk of recurrent SCAD with beta-blocker therapy.144 Current recommendations support the use of beta-blockers in SCAD patients with hypertension to reduce the risk of SCAD recurrence.145 Additionally, there is conflicting evidence regarding the use of statin therapy in patients with SCAD.145 One study even suggested an increased risk of recurrent SCAD associated with statin therapy.145 In the study by Seidl et al., patients with and without MACE did not demonstrate significant differences in medical therapy.145 However, a large portion of patients in their cohort were treated with statins, and there were no adverse outcomes associated with their use.145 Additionally, Clare et al. found no association between medical therapy with antiplatelet agents, beta-blockers, or statins and the risk of recurrent SCAD.58 Franke et al. were also unable to reveal any significant associations between specific medical therapies and a reduction in MACE or recurrent events.146 Patient-Related Outcomes Commonly reported predictors of in-hospital mortality in SCAD patients include a higher comorbidity burden, advanced age, female gender, vessel tortuosity, peripartum SCAD, and history of connective tissue disorders.143 In 2016, Nakashima et al. conducted a study analyzing the long-term outcomes of young female SCAD patients with AMI.62 96 They found that the incidence of MACE was seven times higher in young female SCAD patients than in patients with atherosclerotic AMI.62 Additionally, the most commonly reported cardiac event was recurrent AMI due to SCAD recurrence, 42% of which occurred within 30 days of the initial event.62 In a 2018 analysis of the National Inpatient Sample (NIS) database (2004-2015), Krittanawong et al. reported a significantly higher rate of in-hospital mortality in female SCAD patients compared to males (5.03 versus 3.55%; P < .001).142 STEMI patients also had a higher rate of in-hospital mortality (14.4%), followed by NSTEMI (7.7%) and UA patients (0.99%).142 In contrast, McAlister et al. reported similar in-hospital outcomes and rates of MACE between male and female SCAD patients.107 However, at the clinic follow-up, they found that women had a higher tendency to report chest pain, visit the emergency room for chest pain and get admitted to the hospital due to chest pain.107 In a multicenter study conducted by Saw et al., 8.8% of patients experienced MACEs at the 30-day follow-up, with connective tissue disease and P-SCAD identified as significant predictors.94 MACEs increased to 10–17%, and 13% experienced recurrent SCAD at the 2-year follow up.94 At 3 years, mortality, recurrent MI, and overall MACE were 0.8%, 9.9%, and 14%, respectively, with peripartum SCAD, genetic disease, and extra-coronary FMD identified as predictors of 3-year MACE.94 Patients with postpartum SCAD appear to have a particularly poor prognosis, including larger infarcts and a lower mean LVEF.40 In a study by Chen et al., women with P-SCAD had similar long-term clinical outcomes and rates of recurrence compared to NP-SCAD patients.69,94 However, primary composite MACE outcomes were significantly higher in the P-SCAD cohort (50.0% vs 26.0%), largely influenced by the significantly higher proportion of persistent 97 LVEF reduction at follow up (18.2% vs 5.3%).69,94 Moreover, Al-Hussaini et al. found that P-SCAD was associated with larger infarcts and suggested that the prevalence of proximal dissections and STEMI presentations in P-SCAD may be responsible for the increased infarct size.147 Although traditional CV risk factors are less common in SCAD patients, hypertension has been associated with an increased risk of SCAD recurrence.37,49 In 2018, Rigatelli et al. reported a significantly higher prevalence of hypertension among patients with recurrent SCAD compared to those without (50% vs 13%).37 In a 2017 prospective study, Saw et al. identified hypertension as a significant risk factor for SCAD recurrence.28 Notably, in the same study, the use of beta blockers was associated with a reduced risk of recurrent SCAD.28 Consistent with these findings, a meta-analysis by Chi et al. revealed a 1.5-fold increased risk of recurrent SCAD associated with hypertension, as well as a 50% decreased risk with beta blocker therapy.144 Given that beta blockers are commonly prescribed to manage hypertension, these findings indirectly support the proposed association between hypertension and SCAD recurrence. Moreover, these results also suggest a potential protective effect of beta blocker therapy against the recurrence of SCAD, thereby underscoring the pivotal role of hypertension management in mitigating this risk. FMD and migraine have also been proposed to increase the risk of recurrent SCAD, but evidence is conflicting. Chi et al. reported a 2-fold increased risk of SCAD recurrence in FMD, but no association with migraines.144 In a recent retrospective study by Haque et al., patients with extra-coronary vascular abnormalities (EVAs) were found to have a higher rate of R-SCAD than patients without EVAs.144 Notably, FMD 98 accounted for 88.5% of EVAs.144 Additionally, using a multivariate Cox regression analysis, Clare et al. revealed that the risk of R-SCAD was 5.1 and 3.4 times higher in patients with FMD and a history of migraine, respectively.58,75 In contrast, Inohara et al. did not observe a significant difference in R-SCAD events between patients with and without FMD.106,144 Similarly, in a study by Saw et al., FMD was not found to be a predictor of recurrent SCAD.28,144 Furthermore, in a study by Kok et al., 40% of SCAD patients had a history of migraine, but there was no significant difference in R-SCAD between patients with and with a history of migraines at a 5-year follow-up.37,63 Psychological and Quality of Life Outcomes Posttraumatic stress disorder (PTSD), depression, and anxiety are frequently experienced by patients following MI, especially in young female patients.3,148 In MI survivors, PTSD has been associated with recurrent cardiac events, increased mortality, and decreased quality of life.148 Similarly, depression has also been shown to significantly increase all-cause mortality, cardiac mortality, and recurrent MI.148 Previous studies have reported PTSD, depression, and anxiety rates of up to 15%, 20%, and 30%, respectively, in post-MI pateints.95,148 SCAD is a particularly stressful event and is associated with high levels of psychological distress.3,149 Recent qualitative analyses on SCAD survivors reported fear, anxiety, confusion, loneliness, isolation, and grief as significant challenges following a SCAD event.95,149,150 The rarity of SCAD, its sudden onset, unclear pathogenesis, inconsistent and insufficient management recommendations, potential for recurrence, and limited secondary prevention options create unique challenges for SCAD patients.148,149 Caregiving responsibilities, hormonal changes, peripartum mood disorders, and 99 disruptions to expectations of early bonding and breastfeeding generate additional challenges for postpartum patients.5 Additionally, Many SCAD survivors harbor fears of engaging in physical activities, often stemming from concerns about triggering another dissection, leading to common reluctance or avoidance of physical activity.3,5 Collectively, these factors likely contribute to the high levels of distress, poor quality of life scores, and increased rates of rehospitalization observed in patients’ postSCAD.148,149 Research has shown that SCAD survivors frequently experience symptoms of depression and anxiety.5,148 Risk factors associated with increased psychological symptoms following a SCAD event include female sex, young age, P-SCAD, and low resiliency scores.3 In a 2014 cross-sectional study approximately 40% of patients reported a history of depression and anxiety, and one-third underwent treatment for anxiety and depression following their initial SCAD event.5 Johnson et al. also reported a significant prevalence of depression and anxiety symptoms in post-SCAD patients (41%) in their 2020 analysis.148 In this study, women and young patients were more likely to experience more severe PTSD and anxiety related symptoms.148 Symptoms of depression were also more severe in young patients.148 Moreover, a lower emotional and social quality of life was associated with more severe symptoms of PTSD, depression, and anxiety.148 Furthermore, some research suggests that SCAD survivors exhibit higher levels of psychological distress, depression, worry, anxiety, and tension scores compared to nonSCAD MI patients.5,149 Saw et al. found that SCAD survivors exhibited higher levels of anxiety, distress, and depression than those experiencing traditional MI.95 Similarly, Murphy et al.'s study suggested that SCAD-AMI survivors are more prone to anxiety, 100 depression, distress, and cardiac distress in the six months following their acute event compared to counterparts without SCAD.95 Importantly, the rates of anxiety and depression observed in SCAD survivors surpassed those seen in typical MI populations, with over half classified as anxious and over a third as depressed.95 Furthermore, SCADAMI remained a distinct predictor of these psychological states even after accounting for established risk factors for poor post-event mental health.95 In contrast, studies by Johnson et al. and Murugiah et al. revealed comparable rates of depression and depressive symptoms among survivors of SCAD when compared to other MI populations reported in the literature.95,148 However, baseline rates of stress and depression were already high for patients with typical atherosclerotic MI, potentially explaining the lack of significant differences in stress and depression rates between SCAD and non-SCAD acute MI cases.95,151 Summary SCAD, once rare, is now more recognized, but it is still difficult to accurately gauge its prevalence.3,5,15,56 It is more common in women, especially younger women, and is linked to factors such as FMD and emotional stress.5,9,38,48,57,66,76 The presenting symptoms of SCAD can vary widely, but most cases involve ACS symptoms such as chest pain and elevated troponin levels.37,51 Diagnosing SCAD is challenging and often requires using tools such as ECG, biomarkers, echocardiography, and coronary angiography.17,42,49,101,124 Advanced imaging techniques like OCT and IVUS are crucial for an accurate diagnosis.42,49,85,114,119 Treatment approaches for SCAD vary, with a preference for conservative management in stable cases.137,152 However, in severe cases, PCI or CABG may be necessary.137,152 The prognosis of SCAD is generally good, 101 although long-term complications such as recurrent SCAD, chest pain, and MACE events are relatively common.5,37,58,64,114 Case Study Literature Review SCAD represents a distinct and challenging aspect of cardiovascular disease, particularly as a significant cause of acute MI in young women.85 Our main objective is to highlight the unique vulnerability of young women aged 19-30, who suffer from SCAD through careful analysis of case studies. The overview begins by examining the epidemiology of SCAD emphasizing its prevalence and the demographic characteristics of those primarily affected. Understanding SCAD's pathophysiology, clinical manifestations, predisposing factors, and management strategies is crucial, especially given its distinct treatment approach compared to atherosclerotic ACS.85 The complexity of diagnosing SCAD is further compounded by the similarity of its symptoms to other forms of ACS, alongside the absence of specific biomarkers to differentiate it from atherosclerosis.85 However, it is important to acknowledge that much of the current understanding and clinical guidelines for SCAD are based on retrospective and observational research, often subject to selection, survival, and reporting biases.3 There remains a pressing need for high-level, evidence-based guidance for both acute and long-term care of SCAD patients.3 Our analysis considers the dynamic contributing factors of SCAD development, including hormonal influence, predisposing conditions, and lifestyle factors unique to young women. The case studies selected provide a broad spectrum of patient experiences, highlighting diverse presentations, diagnostic challenges, and treatment approaches 102 specific to SCAD. Through this comprehensive case study analysis, we hope to contribute to a more nuanced understanding and improved management of SCAD in young women, ultimately aiming to enhance patient outcomes in this population. Demographics and Patient Characteristics In our analysis of 23 case studies, we found that the participants had an average age of 26.8 years, ranging from 19 to 30 years, contrasting with other reports where the mean age of SCAD presentation ranged from 44 to 53 years.3,27,85 Though limited, the ethnicity data from our SCAD case studies reflects some diversity with 3 Caucasian, 1 African American, 1 Asian, and 1 Arabic individual among 17 unspecified cases, highlighting SCAD's impact across different ethnicities. Similarly, in broader research, Clare et al.'s study reported a cohort with 86% Hispanic Americans, 33% Black Americans, and 13% Asian.3,58 In comparison, Chen et al. found 49.5% of their SCAD cohort to be nonwhite, including 13.5% Black, 16.2% Hispanic, and 18% Asian patients.133 Additionally, Krittanawong et al.'s study from 2004 to 2015 revealed significant ethnic variation in SCAD incidence among women, with the highest cases in White women (3,775), followed by Black (457), Hispanic (290), Asian (73), Native American (20), and other ethnicities (168).142 Cardiovascular Risk Factors Out of 23 case reports, cardiovascular risk factors were present in 10 patients, with smoking in 5 cases, hypertension and obesity in 3 cases each, and family history in 1 case. This aligns with current research indicating a smoking, hypertension, and family history as the most common CV risk factors in SCAD patients. For example, Adlam et al. (2018) reported hypertension in 17% to 57% of SCAD patients, smoking in 8% to 57%, 103 and family history in 8% to 40%.124 Addtionally, CV risk factors were identified in 3 PSCAD cases. Smoking was the most common and present in 2 cases67,153, followed by hypertension observed in 1 case.154 In contrast, other researchers have cited a more comprehensive array of traditional CAD risk factors, including family history, dyslipidemia, and hypertension, suggesting an even greater risk profile for P-SCAD patients than indicated in our analysis.17,155–157 Higgins et al. reported a variety of factors, with 36% of P-SCAD patients displaying a cardiac risk factor, 23% of patients using tobacco, 16% with a family history of CAD, and 9% and 7% with hypertension and hyperlipidemia, respectively. However, Cano-Castellote et al. noted that SCAD patients with hypertension have similar blood pressure levels compared to their age-matched peers, possibly explaining the low prevalence in our cases.17 Pregnancy-Related SCAD and Oral Contraceptives From our case studies, we observed several SCAD cases related to pregnancy and postpartum (P-SCAD) with 4 pregnant and 10 postpartum patients. Literature reviews show similar incidences and indicate that a significant majority of P-SCAD cases are postpartum, with the remaining occurring during pregnancy.67,70 Additionally, notable literature by Hayes et al. (2020) state that P-SCAD is responsible for about 17% of all SCAD incidents and is a significant cause of AMI during pregnancy.3 Furthermore, Adlam et al. (2018) found that 21-27% of myocardial infarctions occurring during pregnancy and 50% of postpartum coronary events are reportedly caused by SCAD.124 Pregnancy complications were also observed within our case studies, including miscarriage and gestational diabetes mellitus, each complication occurring in 1 case. However, our findings seem to show a lower rate of occurrence than those reported in the 104 general literature. For instance, Tweet et al. (2017). reported preeclampsia occurring in 11% of their patients, far exceeding the U.S. population estimate of 3.4%.66 They also reported gestational hypertension in 19% of patients, with diagnoses of preeclampsia and gestational diabetes mellitus in 11% and 7% of patients, respectively.66 Furthermore, 4 cases reported the use of oral contraceptives, highlighting their potential role as a risk factor. Estrogen-containing oral contraceptives, in particular, have been identified as increasing the risk of SCAD.18,48,73 While several other cases in the literature have reported associations between SCAD and oral contraceptive use, it is important to note that the prevalence of contraceptive use among women with SCAD does not significantly differ from that in the general population.3 This suggests that while oral contraceptives may be a contributing factor, their role in the development of SCAD requires further investigation to fully understand their significance in the context of SCAD risk. Predisposing and Precipitating Factors SCAD has a diverse pathophysiology and is associated with inflammatory disorders and arteriopathies.28,94 According to Kaddoura et al., 62.7% of SCAD patients had fibromuscular dysplasia, 11.9% had systemic inflammatory disease, and 4.9% had connective tissue disorders.28,94 Studies consistently indicate a link between FMD and SCAD, with its prevalence varying between 25% and 86%.5,9,38,48,66,76 Furthermore, Tweet et al. found that 42% of P-SCAD patients showed evidence of FMD compared to 64% in NP-SCAD patients.66 However, only 2 of our case studies were reported to be associated with FMD, however, of note one of those cases experienced cardiac arrest.158 105 In addition, our study found 1 case of SCAD that was associated with a connective tissue disorder,159 while another was linked to systemic lupus erythematosus (SLE).19 Although SLE is relatively rare in SCAD patients (occurring in only about 0.2 to 0.42% of cases), understanding its potential impact on SCAD etiology is crucial in managing this condition.48 These findings indicate a more diverse range of risk factors and conditions associated with P-SCAD than we observed in our cases, underscoring the complexity of this condition. Potential triggers of SCAD, such as emotional or physical stressors, have been identified as the most common factors.3,85,94 Kaddoura et al. reported that emotional stress accounts for 40-50% SCAD events and 24-29% are related to physical or exercise-related stress, while Hayes et al. (2020) stated these to be responsible for triggering events in up to 67% of SCAD patients.3,94 Of our case studies, emotional distress was reported in 2 cases and physical stress was identified in 1 case. The diversity in precipitating factors in our cases, ranging from psychiatric disorders to various forms of stress, underscores the complex interplay of psychological and physiological factors in the development of SCAD. This complexity is further highlighted by the fact that the frequency of patient-reported stressors prior to SCADinduced AMI is significantly higher than in other ACS cohorts.3 These findings emphasize the importance of considering both mental health and lifestyle factors in the risk assessment and management of SCAD, particularly in light of their apparent impact on the onset and progression of this condition.3 106 Coronary Distribution Our analysis showed that the LAD was the most frequent vessel affected by SCAD, implicated in 16 of the 23 cases, while proximal dissections occurred in 13 patients. The LM was involved in 8 cases, all of which was related to multiple vessel dissections, with total multivessel involvement found in 10 cases. The LCX and RCA were also prominent in 7 and 6 patients, respectively. Other coronary arteries included OM branches in 3 cases, diagonal branches and the PDA in 2 cases each, with an AM branch in 1 case. SCAD predominantly affects the LAD, especially its mid to distal sections, in the majority of cases, with multi-vessel disease observed in up to 10-15% of patients.49,85 Multiple studies, including those by Saw et al., Lettieri et al., Nakashima et al., Motreff et al., and Jackson et al., consistently report the LAD as the most frequently involved vessel in SCAD, with a significant proportion of cases showing involvement in its branches.62,64,74,109,160 The LCX and RCA are also affected, but to a lesser extent. Jackson et al. note the LCX as the second-most commonly affected vessel, while the RCA and LM are less frequently involved.109 Studies by Sharma et al. and Ma et al. demonstrate variation in the affected coronary arteries, with the RCA being most affected in Ma et al.’s findings.15,111 This overall trend underscores the LAD's vulnerability in SCAD cases and highlights the importance of focusing on the LAD in diagnostic evaluations and management. 107 Clinical Presentation Acute Coronary Syndrome Our analysis showed that ACS was a universal finding as it occurred in all of our case studies, consistent with the literature reporting that up to 35% of ACS events in women under 50 can be attributed to SCAD.85 13 of our case studies presented as STEMI and 9 as NSTEMI. This high occurrence of ACS in our case studies is in line with the general literature on SCAD, where ACS is a common presentation in around 90% of patients.37,51,64 However, the incidence of STEMI and NSTEMI presentations in SCAD patients varies widely in different studies, ranging from 26% to 87% for STEMI and 13% to 69% for NSTEMI, indicating significant variability.103 While Saw et al. reported NSTEMI in 74.3% and STEMI in 25.7% of SCAD patients, in contrast, Daoulah et al. reported a more balanced distribution of ACS presentations, with NSTEMI and STEMI occurring at rates of 47% and 49%, respectively.28,94 In addition, Sharma et al. reported 57% of their cohort presented as NSTEMI and 43% as STEMI.15 This data suggests that although NSTEMI is the more frequent initial symptom of SCAD, STEMI is also a significant factor. Furthermore, conflicting the data presented by the literature, our analysis demonstrated a greater occurrence of STEMI than NSTEMI. Chest pain was the predominant symptom in our SCAD case studies, reported in 22 out of 23 instances. It was prevalent among patients with STEMI, occurring in 12 out of 13 cases and entirely in all 9 NSTEMI cases. Additionally, radiating pain was noted in 5 STEMI and 3 NSTEMI patients, and dyspnea was experienced by 4 patients with STEMI and 2 with NSTEMI, underscoring the diverse clinical manifestations of SCAD. 108 Comparable to our analysis, the data presented in the literature reports that chest pain is the predominant presenting symptom in 60-90% of SCAD cases.17,49,124 In a retrospective study by Lindor et al., the initial patient presentation in the emergency department was described. Chest pain was frequently observed at 85% of patients.94 Similarly, the Vancouver General Hospital SCAD Clinic reported chest pain in 96% of their 2017 study, with half experiencing pain radiating to the left upper limb.101 Likewise, Saw et al. (2014) noted chest pain was associated with radiation to the arm in 49.5% of patients and neck in 22.1%.114,124 Within our STEMI case studies, elevated troponin levels and reduced LVEF occurred in 9 cases each, while all 9 of the NSTEMI cases presented with elevated troponin levels, but 3 cases exhibited reduced LVEF. Lindor et al.’s study reported that 72% of cases showed an initial increase in troponin levels94 while Saw et al.’s 2019 multicenter observational study reported a prevalence of 97.6%.56 Reduced LVEF was found in 25.6% of these patients, similar to the results of a study conducted by Saw et al. in 2017, where 21.8% of patients exhibited reduced LVEF.28,56 On the other hand, Lionakis et al. reported a reduced LVEF in approximately 44% to 49% of patients.114 The frequency of elevated troponin levels in our case studies coincides with Lindor et al. and Saw et al.'s findings.56,113 However, we observed a higher incidence of reduced LVEF than their reported rates, suggesting a more pronounced occurrence of this ACS symptom in our cases than in broader studies. Furthermore, while evaluating vessel distribution in between STEMI and NSTEMI presentations, we discovered that only one vessel was involved in 9 STEMI and 3 NSTEMI cases. On the other hand, multiple vessels were involved in 4 STEMI and 6 109 NSTEMI cases. According to a study by Tweet et al. (2012), single vessel involvement was reported in 79% of STEMI and 24% of NSTEMI cases, while multivessel involvement was observed in 21% of STEMI and 89% of NSTEMI cases.68 Our analysis demonstrates a greater proportion of multivessel involvement in STEMI cases and a greater proportion of single-vessel involvement in NSTEMI cases, whereas the data presented by Tweet et al. (2012) shows that multivessel involvement is more significant in NSTEMI.68 Severe Presentations In our case studies, we found that severe occurrences of SCAD involved cardiac arrest in 3 cases46,158,161 and cardiogenic shock in 2,153,162 consistent with findings from previous research. For instance, Lionakis et al. found that cardiogenic shock occurs in less than 3% of SCAD cases and Teruzzi et al. reported it in approximately 2%.49,114 Lettieri reported a 2.8% incidence of out-of-hospital cardiac arrest, while Sharma et al. observed cardiac arrest in 12% of SCAD patients, including 4% that occurred out-ofhospital.15,64 Nakashima et al. noted cardiogenic shock or cardiac arrest in 16% of patients, and Giyanani and Som reported cardiogenic shock in 2.2% to 5% of cases.62,103 These reports affirm that although cardiogenic shock and cardiac arrest are relatively rare in SCAD, they are critical conditions that require immediate attention. Additionally, all 3 patients in our case studies who experienced cardiac arrest suffered from ventricular fibrillation. Two patients had STEMI, while all 3 had a reduced LVEF.46,158,161 These findings are comparable to different data reported in the literature. Tweet et al. (2012) reported these arrhythmias in 14% of SCAD patients, mainly associated with STEMI, while Saw et al. identified slightly lower rates of 8.9% and 8.1% 110 in their 2017 and 2019 studies, respectively.28,56,68 Studies by Giyanani & Som and Teruzzi et al. observed ventricular arrhythmias in 3% to 11% and 5% of SCAD patients, respectively,49,101,103 while Lionakis et al. also noted ventricular arrhythmias as a complication in 3% to 10% of their cases.114 Furthermore, Phan et al. reported that a significant difference in reduced LVEF was more common in 45.5% of patients who experienced cardiac arrest compared to 13.2% of those who did not.163 Our cases align with these studies, highlighting that ventricular arrhythmias, particularly ventricular fibrillation, are a severe but less frequent complication of SCAD. Out of the cases that experienced cardiac arrest, 1 patient had a dissection affecting the LAD,46 while 2 additional cases showed dissections in the RCA, 1 of which was in the proximal segment.158,161 However, no multi-vessel involvement was noted, and no dissections were identified in the LM, diagonal, LCX, OM, or PDA in those with cardiac arrest. Phan et al.'s study compared factors associated with cardiac arrest in patients with SCAD. The study found that 36.4% of SCAD patients who suffered sudden cardiac arrest involved the proximal coronary vessel, and 18.2% had LM involvement, a statistically significant higher rate compared to those without cardiac arrest. LAD involvement was observed in 63.6% of these patients. Meanwhile, the rates of LCX involvement at 9.1% and RCA involvement at 27.3% did not differ significantly from the patients who did not have cardiac arrest.163 Pregnancy-Related SCAD Our analysis included 12 cases of pregnancy associated SCAD (P-SCAD), 4 involved pregnant women, and 8 were in the postpartum period. Typically, these patients 111 experienced multiple pregnancies, with an average gravida para of approximately 4 and 3, respectively. Research suggests that women with P-SCAD are typically older at the time of their first childbirth and have had more pregnancies compared to those without SCAD.49 For instance, Higgins et al. found that their P-SCAD patient cohort had an average age of 33.5 years and reported an average of 2.7 pregnancies.155,156 Tweet et al. (2017) noted a significant trend of multiple pregnancies among women with P-SCAD, with 91% having had multiple pregnancies, a rate higher than the 76% observed in NP-SCAD patients.66 Moreover, 80% of the P-SCAD patients were multiparous, compared to 64% in the general U.S. childbearing population, suggesting a more frequent occurrence of multiple pregnancies in women with P-SCAD than in those with NP-SCAD or in the general childbearing population.66 In addition, Saw et al. (2019) documented that 4.5% of SCAD patients experienced P-SCAD during the peripartum period and a significant proportion of these patients were found to have extensive maternity backgrounds.56 Among them, 8.9% had been pregnant five or more times, 8.5% had given birth four or more times, and 2.3% had given birth five or more times, qualifying them as grand multiparas.56 These results suggest a strong link between SCAD and multiple pregnancies or childbirths.56 While our case studies involve a younger average age, our discovery of a history of multiple pregnancies aligns with literature suggesting a higher incidence of P-SCAD in those with a history of multiple births.56,66,156 Cano-Castellote et al. documented that 69.9% of the patients in their study experienced P-SCAD during puerperium, or the first 6 weeks postpartum.17 From our 112 case studies, the average duration before a postpartum event was approximately 11.88 days, aligning closely to the literature presented by Teruzzi et al., demonstrating the increased risk shortly after childbirth. Tweet et al. (2017) observed 89% of women experienced P-SCAD within 12 weeks following delivery, with 70% occurring within four weeks and 54% within the first week.66 Havakuk et al. observed the variation of SCAD presentation across pregnancy and postpartum periods with 72.5% experiencing SCAD during postpartum, ranging from day 3 to day 210 after delivery.157 Likewise, Teruzzi et al. stated that P-SCAD may happen at any point during pregnancy or after delivery, with a higher likelihood of occurrence within the first week following delivery.49. Of the SCAD events occurring during pregnancy, our case studies display an average gestation period of 16.8 weeks, or approximately mid second trimester. Tweet et al. (2017) reported that 2% of P-SCAD events occur during pregnancy following firsttrimester miscarriage and 2% following stillbirth at ~36 weeks.66 Havakuk found that 17.5% experienced SCAD in the third trimester, while only 6% did so during the second trimester.157 Interestingly, the authors do not report the occurrence of any SCAD events within the first trimester.157 Our case studies share similarities with the findings by Havakuk and Tweet et al. related to the timing of SCAD, highlighting the second and third trimesters as more common periods for these events.66,164 All 12 cases of P-SCAD experienced chest pain, underscoring its prevalence as the most common presenting symptom. Additionally, radiating pain and dyspnea were documented in 3 cases each, while 8 cases presented with elevated troponin levels, indicating myocardial damage. Reduced LVEF was observed in 10 cases, however 113 cardiogenic shock was only present in 1 case.153 According to Havakuk et al.'s study, chest pain was the primary symptomatic presentation in 94% of P-SCAD patients, with 80% experiencing typical symptoms of AMI. However, dyspnea was also observed in approximately 28% of cases. They further reported LV function at the initial evaluation was shown as an average LVEF of 40% in 90 patients, with about 45% having an LVEF below 40% and 31% had an LVEF of < 30%.157 In addition, Ito et al. found that although all patients experienced chest pain, 86% also had elevated troponin levels. The study further showed that 57% of patients had associated dyspnea, 29% had heart failure upon presentation, and 14% had an initial presentation of cardiogenic shock.155,165 While Tweet et al. (2017) further illustrated chest pain as a more prevalent symptom in 99% of NP-SCAD patients, compared to 93% of P-SCAD patients, they also noted a distinct difference in cardiac function between the two groups.66 Specifically, the average LVEF was lower in P-SCAD patients, at 46%, in contrast to 53% in those with NP-SCAD.66 Additionally, a higher proportion of P-SCAD patients, 26%, had an LVEF of 35% or less, significantly more than the 10% observed in the NP-SCAD group.66 Similarly, Higgins et al. showed that out of 47 patients, approximately 94% were reported to have experienced additional symptoms, such as dyspnea in 34% and diaphoresis in 30%.155,156 Research has shown that P-SCAD patients have higher rates of STEMI than NSTEMI. Of the 12 P-SCAD case studies in our analysis, all presented as ACS, with 8 cases of STEMI and 3 cases NSTEMI. Higgins et al. revealed that over 80% of P-SCAD patients in the study presented with STEMI.155,156 Comparably, in their study, Havakuk et al. found that among the 115 patients, 75.5% had STEMI, while 24.5% had non- 114 STEMI.157 Additionally, research by Tweet et al. (2017) showed STEMI to be significantly more frequent in P-SCAD at 57% compared to 36% in NP-SCAD. Their data further revealed that NSTEMI occurred in 43% of P-SCAD patients compared to 61% of NP-SCAD.66 Cano-Castellote et al. and Ito et al. also demonstrate similar results, reporting that STEMI occurred in 75-80% of P-SCAD and 57% of NP-SCAD patients.17,155,165 The consistent pattern of P-SCAD presenting more often as STEMI than NSTEMI is illustrated within our cases and across multiple research studies. P-SCAD presents itself with a more severe clinical manifestation in comparison to NP-SCAD.49 Two severe medical conditions, including cardiac arrest and ventricular fibrillation, are included in our evaluation of case studies.158,161 Notably, these incidents occurred during the postpartum period and one presented in conjunction with STEMI. This suggests a possible link between the postpartum period, STEMI, and an elevated risk of cardiac issues for patients with SCAD. Illustrating the occurrence of severe presentations, research conducted by Higgins et al. report that 25% of their patients experienced hemodynamic instability, characterized by symptoms like hypotension, bradycardia, or ventricular fibrillation.155,156 Additionally, Phan et al. found that 5.3% of SCAD patients experienced sudden cardiac arrest, with a higher incidence (27.3% vs 7.1%) in those with P-SCAD compared to NP-SCAD.163 However, a study by Tweet et al. (2017) reported similar rates of cardiac arrest in both P-SCAD and NP-SCAD (9% and 10%, respectively), indicating that such severe complications may occur regardless.66 Moreover, Havakuk et al. found that of their patients with SCAD, 10 required emergency defibrillation due to ventricular fibrillation, 9 of these also presenting with STEMI, further supporting our findings and underlining the idea that STEMI is a 115 significant risk factor for severe cardiac events in patients with P-SCAD.157 Therefore, while severe cardiac events like cardiac arrest and ventricular fibrillation are not commonly present in SCAD cases, they are critical considerations, particularly in the context of postpartum status and STEMI.17 The potential for hemodynamic instability emphasizes the need for careful monitoring and management in SCAD patients, especially those in high-risk categories. The LAD was found to be the most commonly affected artery in 9 of our P-SCAD cases, while the LM was involved in 5. Additionally, the LCX was also involved in 5 cases and the RCA in 4 cases. Furthermore, diagonal and obtuse marginal branches were affected in 2 and 1 case, respectively. Havakuk et al. further illustrate the higher prevalence of LM and multi-vessel involvement in P-SCAD patients.157 They explain that in 60% of P-SCAD patients, a single artery is involved, with the LAD as the culprit in 72% of those incidences, followed by the LM segment in 36% of cases. In addition, 62.5% of cases was shown to involve dissection at the ostial or proximal segments of the arteries.157 Similarly, Cano-Castellote et al. reported that the LAD was affected in a significant 44-80% of P-SCAD cases, followed by the RCA, LM, and LCX. They also noted that simultaneous multivessel involvement, although rare, can occur in up to 19% patients.17 The range in affected segments, from ostial to distal portions, not only illustrates the severity of P-SCAD but also emphasizes the importance of thorough evaluation and precise management in these patients. We also found multiple vessels to be involved in 6 of our case studies, each case exhibiting a unique and complex composition of dissections. Case 6, in particular, presents an extensive array of 116 dissections with the LM extending to the mid-LAD, and the ostial LCX continuing into the OM1 branch, along with the distal RCA also being involved.166 Additionally, other cases also revealed various patterns of involvement in critical arteries such as LM, LAD, LCX, and RCA.153,162,167–169 In their 2017 study, Tweet et al. found important similarities and differences in the involvement of blood vessels between P-SCAD and NP-SCAD.66 The study revealed that P-SCAD had a higher rate of LM involvement in 24% of cases, compared to just 5% in NP-SCAD.66 Additionally, multivessel dissections were more common in P-SCAD, with a frequency of 33% versus 14% in NP-SCAD.66 The research also reported a similar pattern of involvement in the LAD, with P-SCAD affecting 70% and NP-SCAD 60%.66 In terms of the RCA and LCX, both types of SCAD had similar rates of involvement, with RCA affected in 20% of P-SCAD and 13% of NP-SCAD cases and LCX in 15% of P-SCAD and 14% of NP-SCAD cases.66 The findings presented from our case studies representing the presenting factors of P-SCAD is comparable to data from the literature, highlighting that chest pain is a common symptom, with variations in frequency and a more comprehensive range of indications such as radiating pain, dyspnea, and diaphoresis.66,155–157,165 Moreover, our observations align with a discernible trend toward more severe cardiac impairment in PSCAD, evident through reduced LVEF and occasional cardiogenic shock.66,155–157,165 While our cases corroborate literature findings regarding the common involvement of the LAD in P-SCAD, we also noted a high occurrence of the LCX and RCA involvement. Furthermore, the prevalence of multi-vessel involvement in our cases mirrors literature data, emphasizing the intricate and variable vessel distribution in P-SCAD presentations. 117 Diagnosis Despite advancements in the recognition and diagnosis of SCAD, patients still face a high risk of misdiagnosis and premature emergency department discharge, primarily due to their relatively young age and lack of traditional atherosclerotic risk factors.5,42 Additionally, the clinical presentation of SCAD often resembles that of other cardiovascular diseases, making it difficult to accurately diagnose.1,16,17 In patients presenting with ACS, clinical suspicion for SCAD is often prompted by young age, female gender, and the presence of few or no traditional cardiovascular risk factors.5 However, it is important to conduct a thorough differential diagnosis to rule out other possible conditions that could cause similar symptoms.17 This involves considering and eliminating potential causes such as AMI of other etiologies, pulmonary embolism (PE), pericarditis, endocarditis, aortic dissection, musculoskeletal disorders, gastrointestinal reflux disease (GERD), pneumothorax, pneumonia, or cardiac tamponade.17 Among the included case reports, ACS was the most commonly occurring differential diagnosis. Other considerations included AMI, SCAD, PE, aortic dissection, costochondritis, GERD, coronary artery spasm, pericarditis, and takotsubo cardiomyopathy (TTC). Current evidence supports the use of diagnostic tests such as ECG, cardiac biomarkers, echocardiography, CT, MRI, or coronary angiogram alongside angiography to improve diagnostic accuracy.17,170,171 The 12-lead ECG is initial diagnostic examination for patients presenting with chest pain, and should be performed within 10 minutes of triage in the emergency department (ED).17 STEMI is diagnosed based on specific ECG criteria, including significant ST-segment elevation at the junctional point, magnitude criteria related to age 118 and gender, and involvement of contiguous leads, in conjunction with clinical symptoms and elevated cardiac biomarkers like troponin.172 On the other hand, individuals with ACS symptoms and elevated troponin levels, who lack ECG changes consistent with a STEMI, are diagnosed as NSTEMI.173 ECG findings such as transient ST elevation, ST depression, or new T wave inversions are suggestive of NSTEMI; however a normal ECG does not exclude the diagnosis of ACS and NSTEMI.173 Almost all patients with SCAD present with ECG findings consistent with ischemia (i.e. STEMI or NSTEMI).5 All our cases included young (19-30) and female patients, with few or no traditional risk factors. In addition to ACS symptoms, more than half of the patients demonstrated STsegment changes on their EKG. The rest of the patients, except for one, were classified as NSTEMI, with either normal ECG findings, or ST depression, T wave inversions, and nonspecific ST/T wave abnormalities. Although less common, SCAD patients can also present with hypotensive hemodynamic alterations, bradycardia, ventricular tachycardia (v-tach), or ventricular fibrillation (v-fib) and sudden cardiac arrest.3,17 For example, the one patient was not classified as either STEMI or NSTEMI presented with ventricular fibrillation (v-fib) and cardiac arrest. She only experienced a few seconds of chest pain before losing consciousness.161 Her initial ECG revealed v-fib, and after 11 minutes of CPR, return of spontaneous circulation (ROSC) was achieved.161 The following ECG demonstrated STelevation in the inferior leads, but this did not meet the diagnostic criteria for STEMI, however, because CTA ruled out pulmonary embolism (PE) and a cranial CT ruled out intracranial pathology, they considered the possibility of SCAD.161 Two other patients 119 presented with v-fib and cardiac arrest46,158, one with bradycardia174, and one with nonsustained ventricular tachycardia.175 Consistent with current literature, the majority of our cases, 18 of 23, also reported elevated levels of troponin. Troponin is a cardiac biomarker released into the bloodstream when there is damage to the heart muscle, such as during a MI.171 It plays a crucial role in the diagnosis of MI, with a near 100% sensitivity when troponin levels are checked 6 to 12 hours after the onset of chest pain. 171 The levels of troponin start to increase within two to three hours of chest pain initiation and reach a peak between 12 and 48 hours.171 After that, the gradual decline of troponin levels to normal over the next four to ten days helps distinguish MI from other conditions that cause elevated troponin levels.171 NSTEMI’s can present unique challenges, as patients may initially present with negative troponin and no ECG changes.171 However, despite the absence of immediate troponin elevation, an NSTEMI could still be present, as troponin levels may not commence their rise until at least 2 to 3 hours after the initial insult.171 This phenomenon has also been documented in cases of SCAD, particularly when the patient's presentation occurs either early or is delayed.5,85 In Case 11, a 21-year-old woman presented to the Emergency Department (ED) with a 12-hour history of sharp, central chest pain, along with transient shortness of breath during minimal exertion and three witnessed episodes of syncope.159 The initial ECG was normal, but her troponin T level was mildly elevated at 17 ng l−1.159 Her troponin levels increased to 33 ng l−1 after 2 hours, and 731 ng l−1 after 48 hours, 120 prompting consideration of SCAD.159 A CTCA was performed, revealing an occlusion of the RCA extending from the AM branch to the PDA.159 In Case 2, a healthy 26-year-old woman presented to the ED with 1 hour of retrosternal, sharp chest pain radiating to both arms.174 Her ECG demonstrated sinus bradycardia, and initial troponin level was 0.05 ng/mL.174 Despite complete resolution of chest pain, she was admitted for serial troponin checks, with levels peaking at 28.77 ng/mL.174 Transthoracic echocardiography (TTE) and CTCA demonstrated normal biventricular systolic function and coronary arteries without atherosclerotic disease.174 A coronary angiogram on the second day of admission revealed an irregular lesion with an 80% reduction in luminal diameter in the first obtuse marginal branch of the left circumflex artery, suggesting type 3 SCAD.174 These cases underscore the importance of serial troponin monitoring in individuals suspected of experiencing an ischemic event, particularly when troponin is normal upon presentation and there is a high clinical suspicion for SCAD. Given the unique characteristics of SCAD, such as its potential for rapid progression and the absence of traditional risk factors, depending solely on a single troponin measurement at presentation may result in a missed or delayed diagnosis. Serial monitoring offers a more comprehensive understanding of the evolving cardiac injury, allowing clinicians to assess the extent and progression of ischemic damage. It is imperative for clinicians to remain vigilant and consider additional diagnostic modalities if a discrepancy arises between clinical presentation and troponin levels, ensuring a thorough and timely evaluation. While noninvasive assessments contribute significantly to the diagnosis of SCAD, invasive coronary angiography (ICA) remains the gold standard imaging modality for 121 confirming SCAD and should be performed whenever ECG findings demonstrate signs of AMI.17,85,116 Yip and Saw developed a classification system that categorizes SCAD into three types based on distinct angiographic features. Type 1, which represents the pathognomonic appearance, involves an intimal tear allowing contrast to pass through the false lumen, revealing translucent lumens indicative of a false channel.48,85,119 Type 2 SCAD is the most common angiographic pattern, characterized by a long, smooth narrowing exceeding 20 mm, with manifestations such as diffuse stenosis with normal artery segments at the proximal and distal ends (type 2A) or extension to the distal tip of the vessel (type 2B).5,101,114,120 Type 3, the least common, resembles atherosclerotic plaque and poses the greatest challenge for diagnosis.40,121 ICA was reported as the primary diagnostic imaging method in 22 out of 23 of the included cases. However, only 5 cases provided information on the observed angiographic type of SCAD, raising uncertainty about whether this omission indicates a lack of familiarity with angiographic variants or if it was simply excluded from the reports. Notably, among the cases that did specify the angiographic type, 4 out of 5 reported type 2 SCAD, aligning with current findings indicating its predominance. While some cases did not use the Yip and Saw classification, they reported other angiographic features that contributed to the SCAD diagnosis. The absence of atherosclerotic lesions in the affected or other coronary arteries was a frequently reported indicator of SCAD across all cases. This observation is consistent with the angiographic definition criteria for SCAD, which requires the absence of coronary atherosclerosis.174 Other commonly cited indicators included distal tapering, evidence of a dissection plane, radiolucent flap, stenosis of the true lumen, and diffuse luminal irregularities. 122 The Yip-Saw classification, although valuable, does not effectively categorize atypical patterns of SCAD, which can make diagnosis challenging, especially when angiographic features do not neatly fit into the typical three categories.85,101 The introduction of Type 4 SCAD, characterized by total occlusion resembling thromboembolic disease, aimed to address some of these limitations.2,46,101 However, this subtype presents its own diagnostic challenges, requiring specific indicators post-blood flow restoration during PCI to confirm the diagnosis.101 Though not explicitly stated by the authors, four included cases displayed an angiographic appearance consistent with type 4 SCAD.19,162,169,176 In two of these cases, dissections or occlusions occurred in proximal vessel segments, deviating from the typical distal presentation associated with type 4 SCAD.162,169 However, the young age of the patients, coupled with the absence of cardiovascular risk factors, and the lack of CAD during ICA, provided additional support for a diagnosis of SCAD.162,169 Moreover, all four patients presented with a STEMI, which aligns with the observations made in a study by Mori et al. According to their findings, there appears to be a strong link between Type 4 SCAD and STEMI presentation.122 This suggests that Type 4 SCAD may have a distinct clinical presentation and could potentially lead to more severe complications.122 In Case 13, a 19-year-old female presented with an abrupt onset of substernal chest pain and left shoulder pain persisting for 14 hours prior to admission.176 Troponin was elevated at 1.320 ng/mL, and initial ECG demonstrated acute anterolateral wall STEMI.176 Subsequent ICA revealed a complete occlusion of the left anterior descending artery (LAD) at the mid-segment, with no significant calcification observed in any of the coronary arteries.176 Initial attempts to restore blood flow through stenting and balloon 123 dilation at the mid LAD were unsuccessful.176 However, balloon dilatation of the distal LAD successfully restored flow, revealing a dissection and confirming the diagnosis of SCAD.176 This case highlights the diagnostic challenges inherent in type 4 SCAD, emphasizing the need for a nuanced understanding of specific angiographic features. The successful resolution through distal balloon dilatation underscores the importance of tailoring diagnostic and interventional strategies to the unique characteristics of SCAD lesions. It serves as a compelling reminder of the critical role accurate diagnosis and awareness of diverse angiographic presentations play in managing this complex condition. An essential element in the differential diagnosis of SCAD involves the distinction between non-atherosclerotic SCAD (NA-SCAD) and dissections arising from atherosclerotic plaque rupture or induced by catheters.114 The differentiation between SCAD and highly localized noncalcified, lipid-rich plaque rupture or erosion presents significant diagnostic challenges.85 Like SCAD, this condition contributes to ACS in young female patients and may be triggered by vigorous physical activity.85 These lesions also frequently display nonobstructive characteristics prior to the acute event and, if managed without revascularization, can potentially undergo healing, resulting in minimal residual stenosis.85 In such cases, the presence of luminal thrombus becomes a valuable diagnostic indicator.85 While thrombus is typically observed only in cases of occlusive SCAD or in the presence of fenestrations, substantial luminal thrombus or downstream embolization strongly suggests an atherosclerotic etiology.85 Al Mahruqi et al. (Case 9) presented an unusual case of SCAD accompanied by extensive thrombosis. A 29-year-old woman presented to the emergency department with 124 severe chest pain radiating to the jaw and both shoulders.168 While her initial ECG and echocardiogram showed no abnormalities, her troponin levels were significantly elevated.168 Subsequent coronary angiography (ICA) demonstrated a type 2 dissection in the LAD; however, within the following 24 hours, the dissection progressed proximally into the distal LMCA and proximal LCX.168 Despite the identification of high-risk lesions, conservative therapy was continued.168 Overnight, the patient experienced severe and prolonged chest pain.168 A 12-lead ECG demonstrated ST depression in the anterolateral leads, and troponin levels surged to 699 ng/mL.168 Consequently, CABG was performed, revealing a complete dissection of the left coronary arteries, including the stem, with visible intramural thrombosis.168 Intravascular imaging tools, such as IVUS and OCT, play a pivotal role in confirming SCAD diagnoses, especially in complex and ambiguous cases.174 Pretest probability and angiographic features, such as coronary tortuosity or minimal atherosclerotic plaque, can help determine when intravascular imaging is necessary to exclude or confirm SCAD.85 Additionally, it is important to consider the increased risk of iatrogenic dissections associated with intracoronary imaging in fragile SCAD arteries.85 However, the need for accurate diagnosis justifies imaging in most case, as relying on angiography alone may introduce uncertainty.85 Among the 23 cases examined in this study, only 8 utilized IVUS to validate SCAD diagnoses. Commonly reported findings included intramural hematoma, compressive hematoma, thrombus, and intimal flap. Importantly, the use of IVUS was not directly associated with complications reported in any of these studies. 125 In Case 12, a 30-year-old female presented with progressive substernal chest pain radiating to the left arm, and associated diaphoresis.18 Her initial 12-lead ECG revealed sinus tachycardia, and troponin levels peaked at 573 ng/L.18 ICA was performed, revealing thrombus in the proximal LAD, spanning from the ostium to just before the first diagonal branch.18 Subsequent employment of IVUS not only verified the existence of intracoronary thrombus but also facilitated the visualization of an intimal flap at the proximal LAD, situated just distal to the ostium.18 This observation, along with the absence of atherosclerotic disease, firmly established the diagnosis of SCAD.18 Furthermore, when diagnostic uncertainty persists following ICA and intracoronary imaging, alternative imaging modalities like echocardiography, computed tomography angiography (CTA), and cardiac magnetic resonance (CMR) can provide valuable diagnostic insights and aid in differentiating between SCAD and other etiologies of ACS.85,115 For example, TTC, also known as "broken heart syndrome" or stress-induced cardiomyopathy, is an acute cardiac condition characterized by a temporary LV myocardial dysfunction, and is often included in the differential diagnosis for patients with SCAD.37 In fact, SCAD and TTC share many clinical characteristics. Both SCAD and TTC have a predilection for women and can be triggered by emotional or physical stressors.37 They also often exhibit symptoms of ACS, increased levels of troponin, and echocardiographic evidence of LV dysfunction.37,171 It can be particularly challenging to differentiate between these two conditions in cases of LAD dissection, as this can lead to septal and apical wall motion abnormalities that resemble those seen in TTC.115 However, there are certain factors that can help distinguish between these conditions prior to 126 performing a coronary angiogram. For instance, TTC is generally associated with a lower troponin and higher BNP ratio compared to acute myocardial infarction (AMI).177 Additionally, TTC usually exhibits regional wall motion abnormalities beyond a single epicardial vascular distribution, whereas SCAD tends to result in more localized abnormalities.123 Case 16 reports a 28-year-old woman in the 36th week of her second pregnancy who presented with acute chest pain after experiencing psychological stress following her grandfather's death.167 She had no medical history or cardiac risk factors, and her first pregnancy was complication-free.167 Initial 12-lead ECG displayed sinus rhythm with a QS pattern in leads V1 to V4 alternating with accelerated idioventricular rhythm.167 Troponin was elevated at 26 ng/ml and transthoracic echocardiography (TTE) indicated LV systolic dysfunction with reduce EF of 40% and anteroseptoapical akinesia, initially suggesting Takotsubo cardiomyopathy (TTC).167 However, due to pregnancy risks, coronary angiography was deferred.167 On day 5, a cardiac MRI revealed isolated apical akinesia and anterior and apical edema, excluding TTC as a possible diagnosis. This led to the consideration of SCAD and prompted further investigation with ICA.167 In Case 5, a 28-year-old woman presented with substernal chest pain, shortness of breath, bilateral arm numbness, and vomiting several hours after an international flight.178 The initial ECG showed ST-elevation in the anterolateral leads, and her troponin levels peaked at 48.52 ng/ml, prompting an urgent ICA.178 While a mild luminal irregularity was observed in a small diagonal branch, the other coronary arteries appeared normal.178 A ventriculogram revealed a significantly reduced left ventricular ejection fraction (LVEF) with akinesis of the anterior, apical, and inferior walls, and relatively preserved 127 basal territories, consistent with TTC or a resolved MI in the proximal LAD territory.178 However, as neither TTC nor a minor abnormality in the diagonal branch could explain the significantly elevated troponin level, CMR was employed for further evaluation.178 These results demonstrated a mid to distal anterior wall, anteroseptal, and apex myocardial infarction (MI) with late gadolinium enhancement (LGE), strongly indicating MI in the mid to distal anterior wall, anteroseptum, and apex.178 Recurrent symptoms, ECG changes, and an unclear explanation for the MI prompted a repeat angiogram four days later, which revealed extensive SCAD in the LM, proximal to distal LAD, LCX, and first and second diagonal branches.178 These cases underscore the crucial role of multimodality imaging in effectively addressing the challenges associated with diagnosing SCAD. Case 16 illustrated that advanced imaging techniques not only help to confirm the need for subsequent ICA but also have the potential avoid unnecessary invasive procedures, thereby minimizing associated risks. Case 5 emphasized the diagnostic challenges and stressed the importance of employing multiple imaging modalities when the angiographic appearance does not align with the patient’s presentation. In both instances, echocardiography and CMR were instrumental in effectively narrowing the differential diagnosis and prompting further angiographic investigations. Particularly noteworthy is the utility of CMR in delineating myocardial pathology and the diverse etiologies of myocardial infarction with nonobstructive coronary arteries.178 The use of these techniques ultimately contributes to a more informed and tailored diagnostic approach. 128 Treatment / Management Strategies SCAD management currently lacks standardized guidelines, with approaches primarily informed by a blend of expert opinion and limited observational data.58,152,153 The European Society of Cardiology and the American Heart Association endorse a conservative treatment strategy for SCAD, especially in stable patients without ongoing ischemia or hemodynamic instability.17,105,135,137,152 This conservative approach is generally preferred due to the high rate of spontaneous angiographic healing observed in SCAD lesions, typically within a month.124,137 Despite these recommendations, the optimal management strategy for SCAD remains contentious.152 The lack of randomized controlled trials comparing conservative therapy with revascularization methods like PCI leaves significant gaps in evidence.58,137,152 Most studies assessing PCI outcomes in SCAD are small, with limited long-term follow-up.137 Moreover, there is uncertainty regarding the applicability of secondary preventive treatments effective in atherosclerotic ACS to SCAD patients, as no randomized trials currently exist to guide therapy choices.58 As a result, the best medical treatment strategy for SCAD remains a subject of ongoing debate and investigation.58,105,135,137,152 Conservative Medical Therapy In our analysis of 23 SCAD cases, we found that approximately half of our SCAD cases (12 out of 23) were treated medically. This aligns with the significant trend observed by Clare et al., where a notably smaller proportion of SCAD patients underwent revascularization procedures—only 4.3% for CABG and 11.1% for PCI, compared to 17.3% and 56.0%, respectively, in other AMI patients.58 In addition, the study by Hassan 129 et al reported 18.6% of patients were treated with PCI, while 81.4% were treated conservatively during their initial SCAD hospitalization.137 The primary objectives of both short-term and long-term medical treatment for SCAD are to alleviate symptoms, improve short-term and long-term outcomes, and prevent the recurrence of SCAD.21 However, there is a significant shortage of evidence to help healthcare professionals achieve these goals since SCAD has only recently been identified as a crucial clinical condition, and there are no established randomized controlled trials to support an evidence-based approach.21 The ideal application and duration of antiplatelet and anticoagulant therapies in SCAD continue to be subjects of debate.114 Anticoagulants are primarily used acutely during revascularization, with long-term use reserved for cases involving left ventricular thrombus or thromboembolism.114 In the acute management of our cases, heparin, including both unfractionated and low-molecular-weight forms, was used in 5 patients. Aspirin, known for its antiplatelet effects and the most frequently administered acutely, was utilized in 8 cases to reduce clot formation risk. Clopidogrel, its use reported slightly higher in SCAD patients than non-SCAD,58 is often paired with aspirin in a DAPT, was administered in 7 cases.13,17,40,101,135 This combination is recommended to counter prothrombotic activity and prevent thrombosis in SCAD cases, with experts advocating for the continued use of aspirin in conservatively managed SCAD patients.116 Furthermore, post-stenting, patients are typically advised to undergo dual antiplatelet therapy for one year, transitioning to lifelong aspirin monotherapy.114 For conservatively treated patients, initial dual antiplatelet therapy, often combining aspirin and clopidogrel, is recommended.114 130 Although reported to be used more in non-SCAD patients, beta-blockers were used in 5 of the 9 case studies in our analysis.58 They have been shown to effectively reduce coronary wall shear stress, regulate heart rate, lower blood pressure, and decrease myocardial oxygen demand, crucial in reducing the likelihood of disease propagation and recurrence.13,40,101,114,116,174,179 This therapy is typically administered during the acute phase and as part of long-term treatment following SCAD. Statins, utilized in 1 of our cases, however, there is an ongoing debate about the effectiveness of lipid-lowering therapies, particularly after a heart attack or in patients with dyslipidemia, where statins are commonly prescribed.114,175SCAD, characterized by an absence of atherosclerosis, presents a unique challenge, as statins may not be as effective in patients with normal lipid profiles.114 Illustrating this, Clare et al. observed that statin use was significantly lower in SCAD patients.58 Percutaneous Coronary Intervention According to a study by Clare et al., revascularization procedures like CABG and PCI were less common in SCAD patients compared to non-SCAD patients.58 Specifically, CABG was performed in 17.3% of non-SCAD patients versus 4.3% in SCAD patients, while PCI was done in 56.0% of non-SCAD patients compared to only 11.1% of SCAD patients. In contrast, our case studies showed a higher frequency of revascularization procedures, with 14 out of 23 cases undergoing either CABG or PCI. In high-risk SCAD cases, such as those with ongoing ischemia, LM artery dissection, or hemodynamic instability, conservative therapy may not be the best approach.5,137,152 Furthermore, Cano-Castellote et al. specified that when the proximal third of a vessel is severely affected, the most suitable option is to perform PCI or 131 CABG.17 Similar to this recommendation, 13 out of the 23 patients from our case studies underwent PCI, with 3 cases involving the LM and 7 cases affecting the proximal portion of the affected artery. Additionally, more severe cardiac complications such as cardiac arrest and ventricular fibrillation were noted in 2, and cardiac arrest and cardiogenic shock were found in 1 case each, indicating the use of PCI in more critical clinical scenarios. This careful selection stresses the importance of assessing each case individually, ensuring that revascularization is reserved for situations where the benefits outweigh the risks.17,152 Prompt revascularization through PCI or CABG is the recommendation in these settings, however treatment decisions should be based on the patient's coronary anatomy and the expertise of the attending physicians and facility.5 Illustrating this, another patient from our case studies (14) underwent PCI for the proximal portion of the LAD, however the dissected ostial LCX could not be successfully wired, so it was managed medically.169 Hassan et al. conducted a study on SCAD patients, and their findings align with our observations, especially in the context of PCI indications and patient characteristics.137 The study revealed that ongoing ischemia was the most common reason for PCI, affecting 37.7% of patients, followed by ongoing symptoms in 25.3%, ventricular arrhythmias in 9.3%, and hemodynamic instability in 4%.137 Additionally, LM artery dissection and involvement of large arteries were significant factors noted in 5.3% and 18.7% of patients, respectively.137 LVEF also serves as an essential indicator in both studies. In our cases, 8 showed reduced LVEF of less than 50%, with 5 being less than 40%.137 Hassan et al. also 132 reported a significantly lower LVEF in the PCI group, with 40.3% having an LVEF of less than 50%, compared to 18.1% in the non-PCI group, signifying a substantial overlap in the LVEF profiles of patients requiring PCI.137 Our findings complement and reinforce those of Hassan et al., particularly in STEMI presence, troponin levels, and LVEF measures, which are critical factors in the decision-making process for PCI in SCAD patients. Our analysis demonstrated similar findings, with similar indications leading to the decision for PCI. In particular, our analysis exhibited 9 cases with reported elevated troponin levels, which complements the finding by Hassan et al. that the PCI group had higher troponin-I levels.137 Additionally, in our cases treated with PCI, STEMI was present in 8 instances, similar to Hassan et al.’s observation where 50.7% of their PCI group had STEMI, compared to 19.8% in the non-PCI group.137 This is a noteworthy correlation, underscoring the critical role of STEMI in determining the need for PCI in SCAD patients. Furthermore, of the 13 STEMI cases treated with PCI, with 2 involving the LM artery and 6 involving the LAD artery undergoing PCI. In contrast, among the 9 NSTEMI cases, only 1 had LM artery involvement, and 3 had LAD artery involvement treated with PCI. These findings partially align with Faiella and Mulvagh's study, which reported that about one-third of their patients were STEMI cases.105 They found a higher prevalence of LAD dissection of 62.0% in STEMI patients, paralleling our observation of LAD involvement in STEMI cases undergoing PCI.105 However, while Faiella and Mulvagh noted a 6.2% incidence of LM dissection in STEMI patients undergoing revascularization, our study showed a slightly higher percentage of 15%.105 133 Furthermore, when comparing the incidence of LM dissection in NSTEMI patients undergoing revascularization, the 11.1% reported by Faiella and Mulvagh aligns closely with the proportion in our study, where our single NSTEMI case treated with PCI also represents 11.1%.105 Additionally, there is a notable trend of LAD dissection in STEMI patients undergoing PCI in our study and Faiella and Mulvagh's research.105 We also found that pregnancy and postpartum were common factors among 8 patients who were treated with PCI. Feldbaum et al. observed that younger patients, especially those with P-SCAD or SCAD affecting the LM, LAD, or multiple vessels, were more likely to undergo revascularization.134 Additionally, Cano-Castellote et al. suggested that performing PCI or CABG is the most appropriate solution when the proximal third of a vessel is severely affected.17 Coronary Artery Bypass Grafting CABG becomes a crucial treatment option for SCAD in scenarios involving extensive damage to multiple coronary vessels, LM involvement, or proximal region dissections.5,17,114,136 The circumstances of our case studies reflect these recommendations as 6 cases had multivessel disease and LAD artery involvement. In addition, 5 of these cases also presented LM artery involvement, highlighting the importance of the procedure in managing complex coronary artery dissections. In addition, CABG is considered when ischemia persists despite conservative therapy following unsuccessful technical attempts or complications of PCI.5 CABG is a viable treatment option for SCAD patients, especially when PCI is not feasible or has failed.17,40,114,136 This was particularly evident in 3 of our case studies where patients initially treated with PCI later required CABG. The criteria for considering PCI a failure 134 included significant dissection or stenosis after the intervention, a worsening of TIMI flow compared to the initial conditions, or an extending dissection requiring immediate CABG.56 Hassan et al. reported that emergency bailout CABG was required in 5.3% of their SCAD patients.137 Nakashima et al. explained that in some instances, it is impossible to wire into the true lumen distally, leading to emergent CABG.62 5 of the CABG case studies were pregnancy or postpartum related. It has been suggested by a few case reports that CABG may provide some potential complication avoidance common during PCI in P-SCAD such as dissection extension and aneurysm formation.114 However, it has not been clinically proven that CABG is more beneficial than PCI, as no existing trials support this claim.114 Despite the advancements in medical treatments, CABG continues to play a vital role as a therapeutic strategy for critically ill patients by ensuring coronary blood flow and myocardial perfusion. In managing SCAD, there are no standardized guidelines, with current strategies primarily informed by expert opinion and limited data.58,152,153 The European Society of Cardiology and the American Heart Association recommend a conservative approach, especially in stable SCAD patients.17,105,135,137,152 However, the optimal management strategy remains debated due to a lack of comprehensive studies.58,137,152 In our analysis of 23 SCAD cases, less than half received medical management, contrasting with larger trends towards conservative treatment. Revascularization procedures, including PCI and CABG, were more prevalent in our study, employed in 14 out of 23 cases. Notably, CABG was critical in complex cases displaying extensive vessel damage or LM involvement, with 5 related to pregnancy or postpartum. These findings highlight the 135 variability in SCAD management and the need for individualized treatment decisions based on specific patient characteristics and clinical presentations. Outcomes In-Hospital/Short-Term Outcomes In-hospital Major Adverse Events (MAEs) encompass a composite of outcomes, including all-cause mortality, stroke, reinfarction, cardiogenic shock, congestive heart failure, severe ventricular arrhythmia requiring defibrillation or antiarrhythmic agents, repeat revascularization (or unplanned revascularization), and cardiac transplantation.137 Within our selected cases, only 4 instances of in-hospital MAE were observed.162,167,168,180,181 Among them, three cases experienced early recurrent MI167,168,180, two of which involved dissection extension and were initially managed conservatively.168,180 One recurrence transpired approximately 2 days post the initial event168, while the other occurred after 4 days.180 Research indicates that around 5% to 10% of conservatively managed patients may encounter early complications like recurrent MI due to dissection extension, predominantly within the first 7 days post an acute SCAD event, necessitating emergency revascularization.51 Both patients in the cases of dissection extension required urgent revascularization through CABG.168,180 These instances underscore the importance of inhospital monitoring for recurrent ischemia, prompting potential urgent revascularization if conservative therapy fails. A recommended practice involves delaying discharge until day 5–7, allowing for the management of chest pain and recurrent ischemia, optimization of antianginal drugs, and the use of non-invasive ischemia testing as necessary.116 This 136 strategy is particularly crucial since propagation of IMH and additional vessel dissection most frequently occur in the initial days of conservative treatment. 116 Case 16 presented an instance of early recurrent myocardial infarction (MI), attributed to iatrogenic dissection.167 Initial ICA revealed a radiolucent flap in the distal LAD.167 Considering the patient's asymptomatic state and normal coronary flow (TIMI 3), conservative therapy was deemed the most suitable course of action.167 However, during the procedure, the patient developed acute chest pain and significant circumferential ST-segment elevation.167 Subsequent angiography indicated occlusions in the LAD and LCX, likely stemming from a distal LM dissection induced by the guidewire or possibly triggered by flow injection.167 Although PCI was attempted, it achieved only partial success, necessitating emergent CABG.167 This case report underscores the increased arterial fragility in SCAD patients, as well as the iatrogenic risks associated with coronary angiography, particularly during pregnancy.167 SCAD patients are more prone to iatrogenic catheter-induced dissections.137 Guidewire manipulation, angioplasty, or stenting can also propagate dissections Coronary arteries affected by SCAD exhibit heightened susceptibility to iatrogenic catheter-induced dissection. leading to antegrade or retrograde extension during PCI.137 Therefore, careful consideration of interventional techniques is crucial to minimize the risk of complications in patients with SCAD.56 In Case 10, a 30-year-old postpartum woman presented with severe chest pain and ST-segment elevation 1-day postpartum.162 ICA revealed proximal occlusions of the LAD and LCX with the dissection extending back to the ostial LM.162 Cutting balloons were employed to decompress the hematoma, restoring TIMI III flow to the distal LAD; 137 however, the patient developed cardiogenic shock, acute pulmonary edema, and required emergency CABG.162 This case is consistent with current research, highlighting a heightened risk of complications, procedural failure, and suboptimal outcomes in SCAD patients undergoing PCI.58,114 Previous studies suggest that recurrent dissections and high rates of target vessel failure are significant contributors to MACEs following PCI.114 Notably, the Mayo Clinic series reported a 47% procedural success rate, with 13% requiring bailout CABG.110 Moreover, it is crucial to consider that PCI is often performed in patients with higher-risk characteristics, such as STEMI presentations, reduced LVEF, elevated troponin, as well as LM, proximal, and large artery dissections.137 Subsequently these patients also tend to have a worse prognosis, likely due to larger infarctions, higher ischemic burden, severe LV dysfunction, and elevated risks of arrhythmogenicity and heart failure.112 Within 30 days post-discharge, recurrent symptoms, troponin elevation, or both occurred in 4 cases153,169,175,182, with two cases necessitating repeat or unplanned revascularization.153,182 In one instance, the revascularization was prompted by dissection extension, leading to emergent CABG and additional PCI for both native and grafted arteries.153 This case was also complicated by cardiogenic shock, yet no long-term complications were reported.153 Another case reported recurrent MI just 2 days after discharge, likely stemming from dissection extension.175 This closely aligns with previous research which demonstrates high rates of readmission within 30 days postSCAD, often attributed to recurrent MIs, with around half occurring within 2 days of initial discharge.49,75 138 Intermediate/Long-Term Outcomes Following hospital discharge, intermediate and long-term adverse cardiovascular events, including chest pain, depression, anxiety, and MACE such as MI, recurrent SCAD, revascularization, congestive heart failure, stroke, and death, are relatively common.5 Despite this, the selected case reports did not frequently document intermediate and long-term complications, and the majority of cases lacked follow-up beyond six months post-SCAD. Among the reported outcomes, two cases revealed persistent left ventricular dysfunction—one with mildly reduced ejection fraction (42%) and New York Heart Association (NYHA) Class I–II dyspnea on exertion six weeks after discharge162, and the other with an ejection fraction of 35-40%, wall motion abnormalities, and NYHA Class I dyspnea on exertion at the three-year follow-up.169 Importantly, no deaths were observed among the SCAD cases. Women with P-SCAD exhibited more severe presentations (STEMI, v-fib, cardiac arrest), as well as LM (4), proximal (7) and multivessel (4) dissections. Additionally, P-SCAD patients displayed more severe LV dysfunction both immediately and at follow-up, with nearly all cases reporting an initial EF of ≤ 40%, and 5 cases presenting with an initial EF ≤ 25%. Notably, cases of cardiogenic shock were exclusively reported in postpartum women153,162, and 2 out of 3 instances of cardiac arrest also occurred in postpartum women.158,161 Research suggests that patients with P-SCAD face a particularly grim prognosis, marked by larger infarcts, lower mean LVEF, and a higher incidence of life-threatening complications.70,40 They are more likely to present with STEMI, and involvement of the 139 LM, proximal vessels, and multiple vessels is frequently observed in P-SCAD cases.15,49,70 In a study involving 23 women with SCAD, postpartum patients exhibited larger infarcts, more proximal artery dissections, and a lower mean LVEF.5 The Mayo Clinic SCAD Registry findings indicated that patients with P-SCAD tended to be younger, had a higher likelihood of presenting with STEMI and dissections involving the LM and multiple vessels, and demonstrated poorer LV function both immediately and at followup.66 Additionally, in a recent literature review of 120 P-SCAD patients, 73% of patients were postpartum which included 120 cases of pregnancy-associated SCAD, 73% of women were postpartum, 76% presented with STEMI.5 Complications were frequent, and included cardiogenic shock (24%), v-fib requiring defibrillation (16%), and mechanical support (28%).5 The reasons behind the more aggressive and extensive dissections in pregnancy-associated SCAD compared to non-pregnancy-associated SCAD remain unclear. 5 Among non P-SCAD cases, two patients presented with STEMI, reduced LVEF, and more severe vessel distribution, suggesting a potential association between STEMI presentations and vessel distribution, regardless of pregnancy status.176,180 However, there was also a high prevalence of LM, proximal, and multivessel dissections in NSTEMI patients without P-SCAD (N=5), yet they exhibited normal LV function, or minimal dysfunction, and experienced no complications.18,159,182–184 In fact, only P-SCAD patients presented with NSTEMI, high-risk vessel distribution, reduced LVEF, and complications.166–168 This further supports the idea that pregnancy may introduce specific elements that play a role in shaping the clinical course of SCAD patients, independent of 140 other factors like vessel distribution or the type of MI. Additional research is essential to comprehensively investigate the intricate interactions between pregnancy and the outcomes of SCAD. Delays in Diagnosis and Management SCAD patients face an increased risk of misdiagnoses and may be discharged after an emergency department evaluation.5 This is because their comparatively young age and the absence of CV risk factors deviate from the typical profile of patients experiencing atherosclerotic MI.5 A low pretest probability for CAD, could signal a noncoronary diagnosis, potentially leading to a delay in ICA, especially in non-ST-segment elevation myocardial infarction (NSTEMI) patients.116 For example, In Case 14, a 30-year-old woman arrived at the emergency department after 90 minutes of chest pain occurring at rest.169 Despite experiencing ongoing chest pain, she waited for six hours to be evaluated by a physician.169 After undergoing percutaneous coronary intervention (PCI), the patient still suffered a large infarct and significant LV dysfunction.169 Her LVEF remained reduced even at the threeyear follow-up.169 The delay in diagnosis and treatment likely occurred due to healthcare professionals' low clinical suspicion for AMI in a young woman.169 While P-SCAD often leads to more severe arterial dissection patterns with increased morbidity and mortality, an earlier diagnosis and intervention might have led to a smaller infarct and less severe LV dysfunction in this case.169 This case underscores the importance of maintaining a heightened clinical suspicion for SCAD in young women presenting with chest pain, especially those of childbearing age.169 141 The varied angiographic appearances of SCAD can present challenges for accurate diagnosis, causing potential delays in care that may affect patient outcomes. The infrequent occurrence of a "pathognomonic" appearance, coupled with limited awareness among angiographers about nonpathognomonic variants, significantly contributes to under-diagnosis.117 Additionally, SCAD lesions can mimic other MI etiologies, such as atherosclerosis, coronary embolism, coronary spasm, and Takotsubo cardiomyopathy (TTC).3 This overlap further increases diagnostic uncertainty and can have significant short- and long-term implications for patients.3 In Case 5, the lack of significant initial angiographic findings and symptoms overlapping with TTC, led to diagnostic ambiguity, and resulted in a four-day delay in diagnosis.180 Not only did this delay prolong uncertainty for the patient, but it potentially contributed to the extensive progression of the dissection. This highlights the need for heightened awareness of the varying presentations of SCAD and its potential overlap with other cardiovascular conditions. In addition, this case underscores the limitations of relying solely on conventional angiography and emphasizes the potential role of advanced techniques, such as intravascular imaging, in achieving a more precise and timely diagnosis. However, the diagnostic utility of IVUS was limited by the small size of the artery, creating additional challenges for clinicians.180 As a result, they had to rely on angiography to assess the lesion, which made it difficult to identify crucial lumen characteristics that could indicate SCAD. Continuous research and education are crucial to refining guidelines and assisting healthcare providers in effectively recognizing and managing SCAD, ultimately 142 enhancing patient care and outcomes. It is vital to understand the different presentations of SCAD and the potential overlap with other cardiovascular conditions to ensure a timely and accurate diagnosis, leading to appropriate management and improved patient outcomes. Counseling and Follow-up Post-discharge counseling is crucial for patients with SCAD, and should address recurrent chest pain, exercise, and pregnancy.175 While women with a history of SCAD are often advised to avoid pregnancy, recent studies indicate that the majority of those who subsequently conceive experience uncomplicated pregnancies.116 In cases where pregnancy is undesirable, contraceptive methods that avoid systemic estrogen, such as locally acting intrauterine devices, are recommended to minimize hormonal interactions and reduce the risk of SCAD recurrence.116 Comprehensive counseling about contraception is crucial for individuals with a history of SCAD and P-SCAD, aiming to guide the selection of the most effective method with minimal hormonal impact.175 Of 12 P-SCAD cases, only 2 reported pregnancy and/or contraceptive counseling at hospital discharge.166,184 The association between SCAD and acute physical stressors have raised concerns about prescribing physical activity for SCAD survivors.101 However, various case reports and cohort studies have demonstrated the safety and prognostic benefits of cardiac rehabilitation programs in SCAD patients.101,116 Current guidelines advise all survivors of SCAD to enroll in a cardiac rehabilitation program.101 Despite evidence of safety and physical and psychosocial benefits of such programs, current data indicates low rates of both referral to and participation in cardiac rehabilitation.5 Only 1 out of 23 case reports 143 documented referral and participation in a cardiac rehabilitation program153, highlighting the need for increased awareness and implementation of recommended guidelines to optimize the post-SCAD care continuum. Recurrence prevention, medication management, recurrent chest pain, and investigation of SCAD-associated conditions should be addressed at follow-up consultations.116 SCAD is frequently associated with connective tissue disorders, most commonly FMD.175 To comprehensively assess and rule out FMD, connective tissue disorders, and other vascular abnormalities, it is necessary to conduct additional imaging of the head, chest, abdomen, and pelvis.175 SCAD may also be associated with autoimmune and systematic inflammatory diseases such as SLE. 19,83 Most of the documented case reports indicated advising patients to schedule a follow-up and additional screening, but comprehensive details about these follow-up visits were not consistently provided. Completion of FMD screening was mentioned in 2 cases166,169; however, other patients who were advised either they did not follow up or the findings were not reported. Additionally, 2 cases reported a rheumatological work up at followup.19,166 The most effective use of follow-up coronary imaging to guide subsequent management in assessing SCAD healing is still uncertain.185 Therefore, evaluation of LV function is crucial for monitoring the conditions progression and guiding medical and invasive interventions.185 Hayes et al. recommends reassessing cardiac function within 3 months of the initial SCAD event, especially for patients who had LV dysfunction during AMI.3,185 Routine follow-up invasive angiography is discouraged due to the increased risk of iatrogenic dissection in acute SCAD.85 When considering repeat coronary 144 assessment, allowing sufficient time for healing is crucial, usually at least 1 month.85 However, if the patient is asymptomatic, it may be advisable to wait up to 6 months.85 Only 6 cases reported a follow up echocardiogram to assess LV function46,159,162,167,169,186, and 2 cases reported follow up ICA, one at 3 months and the other at 6 months.67,183 Cardiovascular events, particularly SCAD, are associated with high levels depression, anxiety, and PTSD.3 The rarity of SCAD, its sudden onset, unclear pathogenesis, inconsistent management recommendations, potential for recurrence, and limited secondary prevention options contribute to the increased levels of psychological distress, diminished quality of life scores, and hospital readmissions.3,148,149 Notably, women seem to bear a greater burden of these psychological symptoms following both AMI and SCAD.3 Recognizing and addressing the significant psychological impact of an acute SCAD event is crucial for comprehensive patient recovery.3 However, none of the included case reports documented mental health counseling or referral services as part of the long-term management of SCAD patients. This highlights a significant gap in literature regarding mental health considerations in SCAD, underscoring the need for a more comprehensive patient care approach encompassing integrated mental health counseling, tailored treatments, and appropriate referrals to address emotional wellbeing.3 Summary Within our case studies involving SCAD in young women aged 19-30, pregnancy-related SCAD is a prevalent factor, with the LM and LAD arteries commonly affected. A significant challenge in diagnosing SCAD in this group includes the young age of patients and the absence of typical cardiovascular risk factors, often leading to 145 misdiagnosis due to similar clinical presentations to other cardiac conditions and atypical angiographic appearances. Our analysis observed two primary approaches to treatment: medical management and revascularization. Medical management was utilized for patients with hemodynamic stability and no ongoing ischemia, and revascularization procedures like PCI or CABG were used for more severe cases, particularly those with hemodynamic instability, ongoing ischemia, multivessel involvement, or proximal artery dissection. Treatment decisions were also influenced by the effectiveness of initial management or complications during conservative treatment. Regarding clinical outcomes, delays in assessment and treatment significantly impacted both short-term and long-term outcomes. The severity of SCAD presentations, including P-SCAD, vessel distribution, cardiogenic shock, cardiac arrest, and ventricular fibrillation, influenced patient outcomes. Issues such as MACE, early recurrent myocardial infarction, dissection extension, recurrent chest pain, need for repeat revascularization, and reduced LV function were noted. Variations in outcomes and the impact of discontinued care or lack of follow-up were also significant concerns. The findings emphasize the critical need for tailored diagnostic and treatment approaches in young women with SCAD and call for increased awareness and proactive management strategies in this demographic. 146 Chapter 4: Research Method According to recent epidemiological data, there has been a concerning increase in the incidence of AMI among young women, even in those without traditional cardiovascular risk factors.14,21 This shift in cardiovascular disease demographics highlights the need for further research, particularly in young women with SCAD. While numerous research efforts have investigated SCAD’s wide-ranging characteristics, data specific to women aged 19-30 remains essentially unexplored. As a result, there remains a lack of specific data regarding common contributing factors, challenges in diagnosis, optimal management strategies, and outcomes of SCAD in this demographic.21,22 This gap in knowledge heightens the risks of generalized approaches to diagnosis and management, which may not adequately address the unique needs and vulnerabilities of young women with SCAD.21,22 Therefore, it is crucial to bridge this gap in information to improve the understanding and management of SCAD in this population. The purpose of this qualitative analysis is to investigate the common contributing factors, diagnostic challenges, trends in management strategies, and outcomes of SCAD in young women. Utilizing a case study design, this research examines the experiences and medical records of women aged 19-30 who have been diagnosed with SCAD. Case studies were drawn from various peer-reviewed and published works obtained using Google Scholar, PubMed, NIH, and Weber State University’s Stewart Library One Search. Through insights from these case studies, we aim to narrow the knowledge gap, bring essential attention to the occurrence of SCAD within this demographic, and advocate for the most effective approach to managing this disorder in young women. 147 Furthermore, we hope to empower young women to actively advocate for their health, encouraging proactive patient-provider collaboration. Research Questions Q1. What are the common contributing factors for SCAD among young women in this age group? Q2. Are there specific challenges in diagnosing SCAD in young women, and if so, what are they? Q3. What treatment options are commonly utilized in young women with SCAD, and what factors impact the selection of these treatments? Q4. What are the short-term and long-term clinical outcomes for young women with SCAD, and what factors influence these outcomes? Research Methods and Design(s) A case study review is an effective methodology for conducting an in-depth investigation of complex issues within real-life settings, enabling researchers to closely examine the unique characteristics and contextual factors of a specific case or a collection of cases.187,188 This approach is particularly beneficial when exploring SCAD in young women aged 19-30. It provides a flexible and adaptable research design capable of capturing the intricacies and diverse manifestations of SCAD in this demographic.187,188 By comparing patient experiences, presentations, and outcomes across different cases, researchers can generate new insights into the risk factors, triggers, and potential outcomes associated with SCAD in younger women.187,188 Additionally, this method can emphasize the impact of early diagnosis and timely interventions 187,188 The manifestation and management of SCAD involve various components, including its sudden onset, 148 diagnostic challenges, treatment options, and post-diagnosis patient management. 187,188 A case study review can elucidate the challenges inherent to this condition and provide crucial insights into optimal management strategies, thereby informing future research and guiding clinical practice.187,188 Population The population included in this qualitative research consists of young women, aged 19-30, who have been diagnosed with Spontaneous Coronary Artery Dissection (SCAD). Given the rarity and unique nature of SCAD in this age group, the research aims to study the clinical characteristics, underlying conditions, potential triggers, and outcomes for this subset of patients. Unlike typical coronary artery disease, SCAD occurs when a tear forms in a coronary artery, which can lead to myocardial infarction.20,119 Several of these patients may present with unusual symptoms and may not have the typical risk factors associated with coronary artery disease.1,35 This makes their condition particularly challenging to diagnose and manage.1,35 Sample The sample for this study was selected using a purposeful sampling method.54 This technique, common in qualitative research, allows for the selection of cases based on their relevance to the research topic.54 For this analysis, the authors chose to focus exclusively on young women diagnosed with SCAD within the specified age range. The sample size was determined by the availability of relevant case reports and studies. In total, 23 cases were selected for analysis. 149 Data Collection, Processing, and Analysis We executed a systematic search for relevant case reports on SCAD in young women between the age of 19 to 30. Our main resources were Weber State University’s Stewart Library One Search, Google Scholar, NIH, and PubMed spanning the years 2010 to 2023. The search was guided by key terms such as “Spontaneous Coronary Artery Dissection”, “intramural hematoma”, “iatrogenic”, “atherosclerosis”, and “myocardial ischemia”. Both authors engaged in an independent review of the identified studies to ensure alignment with our inclusion and exclusion criteria.54 The subsequent qualitative review adhered to the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) guidelines.55 To be included, case studies had to meet the following criteria: be peer-reviewed, published between 2010 and 2023, and focus on a young woman aged 19-30 with a confirmed non-atherosclerotic SCAD diagnosis unrelated to a recurrent condition. Triangulation was employed to enhance the credibility and validity of this paper by conducting data analysis using a thematic evaluation approach. Both authors independently searched for potential studies to be included and identified and explored themes and patterns across the data set. This provided a variation of perspectives and outcomes within the data set. A first pass descriptive coding technique was used by each author to summarize the content of each study, followed by a pattern coding technique to categorize the emerging themes and patterns.54,189 Assumptions The case studies within this paper are intended to directly address the research questions, offering comprehensive understanding of the contributing factors, diagnostic 150 challenges, trends in management strategies, and outcomes of young women aged 19-30 diagnosed with SCAD.190 These studies contribute valuable insights on the complexities and considerations essential to both diagnosis and management of SCAD in young women. A comprehensive set of studies was organized, with each one undergoing thorough analysis using thematic evaluation and descriptive coding techniques. This approach ensures the reliability of the data presented. To support the credibility and authenticity of our findings, triangulation techniques were utilized. Further, only peerreviewed articles were chosen for inclusion, guaranteeing the validity of our sources.190 The authors emphasize the critical significance of intensely investigating the understanding of SCAD in young women. Not only does it pave the way for more accurate diagnosis and effective treatment but may also develop greater patient education. This stance is further supported by existing literature and preceding studies.190 We acknowledge the potential for biases, stemming from our individual level of professional experience and fundamental beliefs concerning SCAD in young women.187 Nevertheless, we are firm and committed to delivering an analysis that is both balanced and objective.190 To uphold the principles of clarity and integrity, the authors of this qualitative analysis have taken care to transparently outline the assumptions this paper is based on.190 Limitations Our study, built upon a substantial collection of 23 case studies on SCAD in young women aged 19-30, faces certain limitations. A primary concern is the broader lack of research targeting this specific age group, which may directly impact the depth and 151 context of our analysis. SCAD's inherent unpredictability might lead to clinical variability that our sample, despite its size, might not encompass in entirety. The interpretations drawn may carry a preliminary nature due to the paucity of extensive research on this demographic. Additionally, there's an inherent limitation to case studies—they explore deeply but may not always be generalizable to broader trends.187 The quality and depth of data across our collected case studies could vary, potentially influencing the strength of our conclusions.187 Furthermore, the lack of standardized definitions and limited long-term outcomes data add further complexity to our analysis. A significant concern is the potential bias in case study selection; if case studies tend to focus more on severe or unusual SCAD manifestations, our comprehension could lean away from the more typical or more mild presentations.187 Moreover, our study might not account for cultural, regional, or other external factors that can influence the understanding and management of SCAD in this age group.187 Delimitations Our study is built upon a comprehensive review of 23 case studies, all of which focus on young women aged 19-30 diagnosed with SCAD. In terms of publication time frame, we included studies from 2010 up to and including 2023. A notable delimitation of our approach is the exclusive inclusion of case studies written in the English language.191 As a result, we might be missing key insights or findings reported in other languages or emerging from non-English-speaking regions.191 While our primary lens is on SCAD within this particular age demographic, we haven't expanded our scope to encompass related cardiovascular conditions or wider sociocultural or environmental factors 152 potentially influencing this group.191 Only studies that centered on the age range of 19-30 and had a clear-cut diagnosis of SCAD were integrated into our analysis. Ethical Assurances In the scope of scientific inquiry, maintaining ethical rigor is vital, regardless of the nature of the research.192,193 Although our study is a retrospective analysis of previously published case studies and literature, we are aware of the importance of adhering to ethical standards. This section outlines the various ethical considerations we have observed, ensuring that our methodology and design respect the original intentions and contexts of the source studies.192 As described in our sampling methodology, our research exclusively utilized data from published case studies that were publicly accessible. It is essential to emphasize that these original studies had already obtained all required ethical approvals and met the established research standards at the time of their initial publication.192,193 Furthermore, given the retrospective nature of our study, we give our assurance that no direct interaction with human subjects took place. All data were methodically collected from the existing peer-reviewed literature. The case studies included in our analysis did not contain any personal identifiers related to the subjects they described.192,193 Meticulous care was taken to ensure the accurate portrayal of findings from the original cases, avoiding misinterpretation or misrepresentation. As outlined in our methodology, we employed triangulation techniques to support the validity of our analysis.192,193 Our commitment is to maintain utmost transparency in the selection of cases and the sources referenced. All original case studies and data are carefully cited.192,193 In addition, our interpretations and conclusions are distinctly identified as 153 retrospective, acquired solely from available published information. Despite relying on published data, we recognize the potential harm that could arise from misrepresenting or misinterpreting these case studies, which could significantly impact the understanding of SCAD in young women.192,193 We, the authors of this retrospective analysis, declare that no conflicts of interest in relation to the present study exist.192,193 We can affirmatively state that our research's integrity remained uncompromised by external influences, ensuring an unbiased approach throughout the research process. All sources are meticulously cited to respect and acknowledge intellectual property rights. We obtained and secured permissions for any figures, tables, images, or excerpts reproduced within this work.192,193 Summary The methods employed for this qualitative analysis revolved around case studies of young women aged 19-30 diagnosed with SCAD. The selected case studies were chosen based on their relevance and quality, ensuring a robust and comprehensive dataset for analysis. A systematic search, utilizing key terms related to SCAD and this age demographic, was conducted to identify, and systematically categorize these case studies. To ensure the reliability and validity of the findings, triangulation techniques and a thematic evaluation approach were applied. The core assumption behind this analysis is that these case studies can highlight the nuances, challenges, and patterns associated with SCAD in young women, offering invaluable insights for medical professionals and researchers. In addition, our retrospective analysis sought to uphold the highest standards of scientific rigor, transparency, and ethical consideration. While the nature of our study 154 inherently removed certain ethical complexities associated with direct interaction with human subjects, we took every measure to ensure accuracy, transparency, and respect towards the original sources. Our findings, interpretations, and conclusions aim to contribute meaningfully to the understanding of SCAD in young women, all while upholding the integrity of the research process and the contributions of prior researchers in this field.192,193 155 Chapter 5: Findings This paper investigates the experiences, challenges, and prevention of SCAD among young women aged 19-30. The main focus is identifying common factors contributing to SCAD, diagnosing difficulties, and suggesting preventive measures specific to this age group. The research will use a case study design to analyze the personal experiences and medical records of young women who have been diagnosed with SCAD. The aim is to enhance the understanding of SCAD and its unique aspects in this demographic, address any knowledge gaps, raise awareness about its occurrence in young women, and recommend effective management strategies. Our qualitative analysis of SCAD in young women aged 19-30 addresses four key research questions. The findings provide comprehensive insights into this condition's contributing factors, diagnostic challenges, treatment options, and clinical outcomes. Results The first research question aimed to identify common factors contributing to SCAD in young women aged 19-30. Our data analysis revealed that pregnancy-related SCAD was prevalent. Out of the total 23 cases analyzed, 12 exhibited SCAD occurrences associated with pregnancy. Furthermore, the analysis showed that specific coronary arteries were affected, with LM and LAD arteries being predominantly affected in these cases. Our analysis revealed several obstacles regarding the second research question of diagnosing SCAD in young women. One of the primary challenges is the young age of patients. Another significant barrier is the lack of conventional cardiovascular (CV) risk factors typically used to guide the diagnosis of ACS. All patients were 30 years old or 156 younger and had little to no CV risk factors. Smoking was the most prevalent (n=6), followed by hypertension (n=3), obesity (n=3), and family history (n=1). Additionally, of the 10 patients who exhibited CV risk factors, only 2 had more than one. A third challenge demonstrated in the case studies is the clinical presentation of SCAD in young women resembles several other cardiac conditions. Similarly, our analysis also found that the angiographic appearance of SCAD in young women often mimic several other coronary conditions. Moreover, atypical presentations of SCAD that closely imitate other cardiac pathologies were also observed. In examining the third research question concerning treatment options commonly used in young women with SCAD and factors influencing treatment selection, we found two primary approaches: medical management and revascularization procedures, each chosen based on specific clinical scenarios. Medical management was treatment of choice in 12 of 23 cases. It was often employed in cases where patients exhibited hemodynamic stability and the absence of ongoing ischemia. This conservative approach was also preferred in situations marked by diagnostic ambiguity. Conversely, revascularization procedures, including PCI or CABG, were employed in more severe cases. Recommendations for these invasive methods included high-risk SCAD presentations, such as hemodynamic instability, ongoing ischemia, multivessel and left main coronary artery involvement, and dissection of the proximal segment of the affected artery. The decision for revascularization was also influenced by unsuccessful medical management or failed PCI attempts. Procedural complications during initial conservative management or PCI attempts further necessitated the shift to 157 more aggressive treatment strategies. Out of 23 patients, PCI was performed in 13 and CABG was performed in 6. Additionally, 4 of conservatively managed patients required revascularization, and 3 patients treated with PCI required CABG bailout or repeat revascularization. In addressing the fourth research question concerning short-term and long-term clinical outcomes for young women with SCAD and the factors influencing these outcomes, our observation revealed several concerns. It is important to note that there was a significant variation in both short-term and long-term outcomes. One of the most critical factors affecting both short-term and longterm results was the delay in assessing and treating the condition. Additionally, the type of treatment administered, whether conservative management or aggressive revascularization, played a critical role in determining the disease's immediate and future clinical course. The severity of SCAD varied widely among the cases, with factors such as PSCAD, vessel distribution, cardiogenic shock, cardiac arrest, and ventricular fibrillation influencing outcomes. P-SCAD was associated with more severe presentations, such as STEMI, v-fib, and cardiac arrest, as well as high risk vessel distribution. Additionally, PSCAD patients displayed more severe LV dysfunction both immediately and at followup. Almost all cases reported an initial EF of ≤ 40%, and 5 patients presented with an initial EF ≤ 25%. Notably, cardiogenic shock was exclusively reported in postpartum women (n=2). The majority of patients presenting with cardiac arrest (2 of 3) were also in the postpartum period. 158 Regarding the outcomes of patients who had undergone treatment, specific problems were observed regarding in-hospital and short-term outcomes. These issues included MACE, recurrent myocardial infarction (MI), extension of dissection, recurrent chest pain, and the need for repeat or unplanned revascularization. Only 4 patients experienced in-hospital MACE, of which 3 experienced early recurrent MI with 2 as the result extension of dissection. Additionally, within 30 days post-discharge, recurrent symptoms, troponin elevation, or both occurred in 4 cases, and 2 cases required repeat or unplanned revascularization. Furthermore, a small portion of patients experienced persistent LV dysfunction during intermediate and long-term periods (n=2). However, it is important to note that many cases reported a discontinuation of care or did not document follow-up findings. Evaluation of Findings The study's qualitative analysis of SCAD in young women aged 19-30 can provide valuable insights and make incremental contributions to academic and clinical fields. Its uniqueness lies in its focus on a demographic often underrepresented in cardiovascular research. Pregnancy-related SCAD is remarkably prevalent in young women and often affects the LM and LAD arteries. This aspect is crucial as it helps us understand a significant contributing factor of SCAD within this age group, emphasizing the need for healthcare professionals to be aware of this condition. In practice, this understanding can help develop targeted screening and preventive strategies for pregnant and postpartum women, which can help in the early identification and management of SCAD. 159 The study has demonstrated some diagnostic challenges when identifying cardiac events in young women, such as the young age of patients and atypical presentations of SCAD. It highlights the need for a more nuanced approach to diagnosing such events, indicating that more than reliance on conventional cardiovascular risk factors may be required. These findings are significant for clinical practice, as they suggest that the medical profession should develop and adopt more comprehensive diagnostic criteria that consider these unique presentations. Developing treatment strategies based on clinical scenarios can help create a more personalized approach to managing SCAD. While medical management is generally preferred for stable cases, more severe presentations may require revascularization procedures. However, due to the critical nature of timely and appropriate intervention in SCAD, it is necessary to develop individualized treatment plans based on each patient's unique clinical presentation and response to initial therapy. This practical approach can guide clinicians in decision-making, resulting in more effective and tailored care for young women with SCAD and potentially improving outcomes. It is essential to explore the factors that affect short-term and long-term outcomes, such as treatment delays and the severity of the condition. This information helps clinicians prioritize timely assessment and treatment, which could change the course of the disease. Moreover, by observing the different outcomes based on treatment type and follow-up care, we can develop post-treatment strategies that emphasize the significance of ongoing monitoring and support. 160 Summary This study provides new insights into SCAD in an under-researched demographic. It emphasizes the vital role of demographic-specific factors in diagnosing, treating, and managing SCAD. These findings will impact future research directions, clinical practices, and perhaps even policymaking in women's cardiovascular health. They draw attention to the significance of personalized, context-specific approaches for patients. 161 Chapter 6: Implications, Recommendations, and Conclusions The escalating incidence of AMI among young women, particularly those lacking typical CAD risk factors, indicates a considerable shift in cardiovascular disease demographics. Despite extensive research on SCAD, specific data on women aged 19-30 is severely limited, creating a disparity between available information and a nuanced understanding of the challenges faced by this clinical demographic. This qualitative analysis addresses this gap by exploring contributing factors, diagnostic challenges, management trends, and outcomes through a case study design. Based on 23 case studies, the authors acknowledge limitations, including the broader lack of research in this age group, potential selection bias, and the inherent variability of SCAD. Ethical considerations are paramount, ensuring transparent and responsible use of previously published case studies while affirming the absence of conflicts of interest. The following section outlines implications, recommendations, and conclusions from this comprehensive SCAD examination in young women aged 19-30. What are the common contributing factors for SCAD among young women in this age group? In identifying common contributing factors, we observed that out of 23 cases of SCAD in this clinical demographic, 12 cases were P-SCAD, particularly in the postpartum period. This finding aligns with existing literature, which emphasizes the postpartum period as a crucial time for SCAD risk.72 The prevalence of P-SCAD in the postpartum period highlights the necessity for increased awareness and monitoring of cardiovascular symptoms in postpartum women. Additionally, we discovered that PSCAD cases tend to be more severe than non-pregnancy-related SCAD (NP-SCAD). It is 162 common for P-SCAD cases to affect major coronary arteries, such as the LAD and LM arteries. This finding is also consistent with the research, which suggests that P-SCAD may be more likely to involve critical coronary arteries, leading to more severe clinical symptoms.72 This information is significant for healthcare providers as it highlights the need for prompt and thorough cardiovascular assessments in postpartum women with relevant symptoms, regardless of age or traditional risk factors. The high incidence and severity of P-SCAD among young women emphasize the need for improved diagnostic protocols and treatment strategies, particularly for this patient group. Given the potential for severe outcomes and the distinct pathophysiological characteristics of P-SCAD, clinicians should consider a more aggressive approach to diagnosis and prompt management in postpartum women presenting with chest pain or other symptoms suggestive of cardiac distress. Furthermore, these findings can be helpful for healthcare providers, particularly obstetricians, general practitioners, and emergency medicine specialists, to be aware of the higher risk of SCAD in postpartum women. This knowledge can result in enhanced critical monitoring and prompt intervention, with a good possibility of leading to better outcomes for this group. Are there specific challenges in diagnosing SCAD in young women, and if so, what are they? It is commonly believed that young women are at a low risk for CAD, which can lead to a lack of awareness of SCAD. This can complicate early recognition since SCAD in younger individuals is often overlooked, resulting in a delay in diagnosis. This delay can result in disease progression, which can negatively impact the prognosis. Therefore, 163 clinicians should always keep SCAD in mind as a potential diagnosis when young women present with cardiac symptoms, even in the absence of traditional risk factors.161,162 In some of the case studies, the angiographic appearance of SCAD resembled other coronary conditions, such as Takotsubo cardiomyopathy and thromboembolism, underscoring the need to carefully interpret angiographic images and adjunctive imaging techniques, such as intravascular imaging, to differentiate SCAD from other coronary pathologies.123 In addition, the clinical manifestations of SCAD are varied and require a thorough evaluation for accurate diagnosis. Due to the range of symptoms and presentations, there is a risk for misdiagnosis, which can delay the appropriate treatment. Therefore, it is crucial to conduct a comprehensive clinical assessment of young women who exhibit symptoms suggestive of cardiac distress. Differentiating SCAD from coronary vasospasm, thromboembolism, or atherosclerotic plaque rupture is challenging, especially when considering nonatherosclerotic SCAD. Understanding the nuances in angiographic findings is essential for accurate diagnosis. What treatment options are commonly utilized in young women with SCAD, and what factors impact the selection of these treatments? The treatment options for SCAD in young women require a critical decisionmaking process between medical management and revascularization techniques. We found that medical management was predominantly chosen in cases where patients displayed hemodynamic stability and no ongoing ischemia. This approach aligns with the conservative treatment strategy widely recommended for SCAD, intending to minimize 164 the risks associated with invasive procedures while capitalizing on the potential for spontaneous healing of SCAD lesions. However, case studies like those presented by Al Mahruqi et al. demonstrate the complexity of SCAD presentations and the potential life-threatening progression of the disease.168 In a severe and rapidly evolving cardiac case, a young woman presented with distressing symptoms, including intense chest pain. Initial tests failed to show apparent abnormalities, but elevated troponin levels suggested a severe underlying condition. Diagnostic imaging soon revealed SCAD, initially identified in the LAD but quickly spread the LM and LCx arteries. Despite initial conservative treatment, her condition worsened significantly, necessitating urgent surgical intervention. Emergency CABG revealed extensive arterial dissection, highlighting the severity and rapidly progressive nature of her condition.168 As in the example above, situations where SCAD presents symptoms such as ongoing ischemia, significant ECG and cardiac biomarker changes, and hemodynamic instability, more aggressive intervention strategies should be employed if conservative management fails.166 Revascularization techniques such as PCI and CABG are utilized based on the severity of the patient's clinical condition and the complexity of their coronary artery involvement.166,186 In particular, the involvement of major coronary arteries such as the LM and LAD, as well as multivessel disease, were linked to more severe presentations, influencing the choice towards revascularization procedures.162 These findings highlight the importance of a nuanced approach to SCAD treatment, 165 emphasizing the need to individualize therapeutic strategies to specific clinical scenarios and patient responses to initial treatments. The practical significance of these findings is that they can potentially be applied in clinical setups to improve the management of SCAD in young women, thereby enhancing patient outcomes. These insights could also prove valuable in educational programs for healthcare professionals, emphasizing the need to tailor treatment plans for each patient through consideration of their unique disease characteristics. Such an approach can improve clinical outcomes and broaden the impact of our study by contributing to a more comprehensive and informed approach to SCAD management in the broader social context. What are the short-term and long-term clinical outcomes for young women with SCAD, and what factors influence these outcomes? SCAD symptoms can be similar to those of other cardiac conditions. Therefore, the delay in treatment can lead to misdiagnosis or delayed diagnosis, which can severely affect the patient's outcomes. For example, in one of the case studies, there was a significant delay in assessing and treating the patient, which resulted in a substantial myocardial infarction and persistent left ventricular dysfunction despite PCI.169 This case emphasizes the importance of promptly evaluating and intervening in suspected SCAD cases to prevent severe complications and improve outcomes.169 The selection of the most appropriate therapeutic approach for treating SCAD depends on various factors, such as the characteristics of the SCAD presentation, including vessel involvement, P-SCAD, cardiogenic shock, and cardiac arrest. This decision plays a crucial role in determining both short-term and long-term outcomes. In 166 the short term, MACE, recurrent chest pain, and recurrent myocardial infarction were factors noted as factors contributing to the initial presentation severity of some of the SCAD case studies. In addition, persistently reduced LVEF was a significant issue regarding longterm outcomes. However, our cohort involved several cases demonstrating a lack of follow-up or discontinued care. One case study, in particular, illustrated the importance of comprehensive counseling and long-term follow-up for patients with SCAD. She was strongly advised on reproductive health since a pregnancy would be life-threatening due to her exceptionally high risk for a recurrent event.166 Without ongoing medical supervision and proper follow-up care, patients are at an increased risk of adverse outcomes such as recurrence of SCAD and progression of cardiac dysfunction.58 These insights have significant implications for clinical practice in terms of practical utility. They highlight the need for healthcare professionals to be vigilant when assessing young women who present with cardiac symptoms. SCAD should be considered a potential diagnosis in such cases, especially if traditional cardiovascular risk factors are absent. Summary This study contributes to our understanding of SCAD in young women, highlighting the essential need for timely and accurate diagnosis, appropriate treatment selection, and ongoing patient monitoring. These insights are vital for developing more effective guidelines and protocols tailored to manage SCAD in young women, ensuring that treatment decisions consider each patient's unique circumstances and disease characteristics. 167 The findings emphasize the importance of educating healthcare professionals about SCAD, particularly regarding early diagnosis, treatment options, and the necessity of long-term follow-up. Enhanced awareness and education within the medical community could improve recognition and management of SCAD, potentially resulting in better outcomes for young female patients. Moreover, the study underscores the value of public health initiatives to raise awareness among young women about SCAD's signs and symptoms. Educating the public about the importance of prompt medical attention could be a critical step in improving early diagnosis and treatment. The study's implications extend beyond clinical practice, suggesting a broader impact on public health strategies and healthcare education. By understanding the unique challenges in diagnosing and managing SCAD in young women, healthcare systems can implement more effective approaches to increase awareness, education, and training among clinicians and the public, ultimately enhancing care for this specific patient group. Recommendations Given the prevalence of P-SCAD in this age group, multi-disciplinary providers and obstetricians should develop targeted screening and preventive strategies for pregnant and postpartum women. This could include increased vigilance and monitoring of cardiovascular symptoms during and after pregnancy. The diagnostic challenges associated with P-SCAD underscore the need for more comprehensive diagnostic criteria that account for the unique presentations and lack of traditional risk factors in young women. Therefore, healthcare providers should develop individualized treatment plans for SCAD patients based on their clinical presentation and 168 response to initial therapy. This personalized approach should guide clinicians in decision-making between conservative management and aggressive revascularization procedures. Early assessment and treatment in suspected SCAD cases are crucial to prevent disease progression and improve outcomes. The study's findings highlight the impact of treatment delays on patient outcomes, underscoring the need for timely assessment and treatment. Post-treatment strategies emphasizing the significance of ongoing monitoring and support are essential in managing the long-term outcomes of SCAD. These strategies are essential in managing the reduced left ventricular function and the risk of recurrent events associated with SCAD. In order to improve the understanding and management of SCAD among healthcare providers, educational programs that emphasize early diagnosis, appropriate treatment selection, and long-term follow-up should be developed. Public health campaigns aimed at educating young women about the signs and symptoms of SCAD and the importance of seeking timely medical attention could improve early diagnosis rates and treatment outcomes. Future research should focus on exploring the underlying mechanisms of PSCAD, improving diagnostic accuracy, and evaluating the effectiveness of different treatment strategies in young women. Research should also investigate long-term outcomes and the best practices for follow-up care in this demographic. 169 Conclusions Our review of case studies involving SCAD in young women between the ages of 19 and 30 shows a significant increase in AMI, which indicates a change in the demographics of cardiovascular disease. We conducted a qualitative analysis based on 23 case studies, addressing this group's lack of specific data and exploring the contributing factors, diagnostic challenges, management strategies, and patient outcomes. Our findings emphasize the prevalence of P-SCAD, especially in the postpartum period, with a tendency to be more severe than non-pregnancy-related SCAD. P-SCAD often affects major coronary arteries like the LAD and LM. Furthermore, we advocate for improving awareness, monitoring, and treatment strategies for postpartum women. It is essential to have more nuanced diagnostic approaches that consider the unique presentations in young women, even those without traditional risk factors. The study also highlights the significance of individualized treatment plans that balance conservative management and aggressive revascularization procedures based on the patient's condition and response to initial treatments. The study has proposed several recommendations to improve the screening, diagnosis, and treatment of SCAD in women, particularly during pregnancy and the postpartum period. It suggests developing targeted screening and preventive strategies for pregnant and postpartum women to identify those at high risk of developing SCAD. The study also emphasizes the need to enhance the diagnostic criteria to capture unique SCAD presentations in young women, which could help in early diagnosis and prompt treatment. Furthermore, the study emphasizes the importance of timely assessment and 170 treatment to improve outcomes for women with SCAD. These recommendations could help in reducing the mortality and morbidity associated with SCAD in women. The study suggests the importance of post-treatment monitoring and support, educational programs for healthcare professionals focusing on early diagnosis and appropriate treatment selection, and public health campaigns to raise awareness about SCAD among young women. Future research directions should focus on understanding the mechanisms of PSCAD, refining diagnostic accuracy, assessing treatment effectiveness, and exploring long-term outcomes in this demographic. The study contributes significantly to the field by providing insights into the challenges of diagnosing, treating, and managing SCAD in young women, potentially impacting future clinical practices and public health strategies. 171 References 1. Nepal S, Bishop MA. 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