Coronary Artery Dissection and Myocardial Infarction With Nonobstructed Coronary Arteries: Insights From a UK Nationwide Autopsy-Based Registry-Brief Report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and myocardial infarction with nonobstructed coronary arteries (MINOCA) are increasingly recognized causes of acute coronary syndrome and potentially of sudden cardiac death (SCD). SCAD has been correlated to coronary fibromuscular dysplasia (FMD), but the prevalence of SCAD and FMD among SCD victims is unclear. Therefore, we sought to assess characteristics of decedents with SCAD found at autopsy and to compare their clinical and pathological profile with MINOCA victims. METHODS: We reviewed a database of 5325 consecutive cases of SCDs referred to our cardiac pathology center between 1994 and 2017. RESULTS: We identified 18 (0.3%) cases with SCAD and 37 (0.7%) with MINOCA. No signs of coronary FMD were found among SCAD and MINOCA victims. Compared to MINOCA, SCAD decedents were mostly females (78% versus 38%, P=0.006) and SCD occurred during peripartum more frequently in SCAD rather than MINOCA female victims (28% versus 3%, P=0.012) Infarcted myocardium was identified in all cases of MINOCA but only in 5 (28%) of SCAD decedents (P<0.001). Premortem cardiac symptoms were present in 100% of SCAD and 49% of MINOCA victims (P<0.001); substances use or abuse was reported in none of SCAD versus 43% of MINOCA decedents (P=0.001). CONCLUSIONS: SCAD and MINOCA are rare causes of SCD. At autopsy, coronary FMD is not present among SCAD victims. Compared to MINOCA, SCAD victims are more frequently females, are linked to pregnancy, and always experienced premortem cardiac symptoms. Among MINOCA victims' substance use or abuse is common.

Psychosocial impacts of spontaneous coronary artery dissection: A qualitative study.

Spontaneous coronary artery dissection (SCAD) is an increasingly recognised cause of acute myocardial infarction, particularly in younger women without classic cardiac risk factors. While recent quantitative studies have noted high anxiety and depression in SCAD survivors, the full range and extent of psychosocial impacts of SCAD is unknown. The present study used a qualitative approach to investigate the psychosocial impacts of SCAD in Australian SCAD survivors. Focus group participants were recruited as part of a larger study of SCAD survivors currently being undertaken by the Victor Chang Cardiac Research Institute. Thirty SCAD survivors participated in one of seven online focus groups, conducted using a semi-structured format. Focus group duration was 1.5 hours. Each was digitally recorded and transcribed. Data were analyzed thematically according to recommended guidelines. One over-arching theme, five main themes and 26 sub-themes were identified. The over-arching theme related to lack of information, while the five main themes related to emotional impacts, issues with self-management, issues with family, impacts on work life, and the need for psychosocial support. The 'emotional impacts' theme comprised 11 sub-themes, namely shock and disbelief, confusion and uncertainty, unfairness, fear and anxiety, loss and grief, isolation and loneliness, guilt, invalidation and embarrassment, depression, vulnerability, and frustration. Findings are discussed in light of relevant psychological theories. This qualitative study extends previous quantitative investigations of SCAD survivors by providing an in-depth understanding of the complex, inter-related and highly distressing impacts of SCAD. The findings point to the urgent need for a coherent approach to information provision, the development and delivery of SCAD-specific cardiac rehabilitation programs, and the provision of psychosocial support programs for SCAD survivors.

Spontaneous coronary artery dissection: a systematic review of physical and psychosocial recovery following discharge from hospital.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is increasingly recognized as an important cause of myocardial infarction, particularly among women. Spontaneous coronary artery dissection survivors may not know what physical activity is safe and effective, and there may be a psychosocial burden of living with a SCAD diagnosis. OBJECTIVES: This review aimed to determine the evidence regarding physical activity, cardiovascular risk factors, or associated factors, and the psychosocial impact of SCAD for SCAD survivors after hospital discharge. DESIGN: A systematic review was completed in accordance with PRISMA guidelines. DATA SOURCES: We searched Medline, Embase, CinAHL, PsychInfo, and Google Scholar until November 2021. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Outcomes of interest were physical activity participation levels, cardiovascular risk factors and associated risk factors, and psychosocial recovery from SCAD. We included any study (qualitative or quantitative) that reported data pertinent to understanding the impact of SCAD on physical activity and psychosocial aspects of recovery. We also included papers that reported cardiovascular risk or associated risk factors where studies reported outcomes of SCAD survivors. We excluded papers that only provided information on in-hospital management. Any reports that were non-empirical were excluded. RESULTS: The review included 28 studies. These used a range of methods. None were randomized controlled trials. There were 4167 SCAD participants although some were sourced from the same SCAD registries, so they may not be unique. They were mainly female (n = 3897, 93.5%, range = 57.7-100%), with mean age 48.0 ± 9.8 years at index event. Participants mostly came from the USA, Canada, or The Netherlands. We found very limited evidence for cardiorespiratory fitness improvements following cardiac rehabilitation (CR). Existing CR was not tailored to SCAD specific needs and SCAD survivors lacked guidance about appropriate physical activity. Some participants had high levels of psychosocial distress. Spontaneous coronary artery dissection survivors highlighted the need for tailored support that included family members. Many SCAD survivors have traditional risk factors including hypertension, hyperlipidaemia, and overweight/obesity. Chest pain following SCAD is common. CONCLUSION: There is an urgent need to develop physical and psychological recovery programmes for SCAD survivors and test effectiveness via randomized controlled trials. Psychosocial support is particularly required, given the high burden of psychosocial issues. DATA REGISTRATION: Prospero CRD42021254798.

Younger Age Impacts Perceptions of Care Received in the Emergency Department Among Women with Spontaneous Coronary Artery Dissection.

Background: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic etiology of acute coronary syndrome (ACS) that primarily affects younger women with few traditional cardiovascular disease risk factors. The primary objective of this study was to evaluate how younger age impacts the perception of care women receive in the emergency department (ED) at the time of their first or only SCAD. Methods: SCAD survivors were recruited using SCAD Alliance social media platforms to complete a one-time online survey regarding their experiences of seeking treatment for SCAD in the ED and their post-SCAD recovery. A total of 409 participants consented to participate in the parent study and data collected from the 367 participants who reported female gender were further analyzed. Results: Fewer participants <50 years old than would be expected under the null hypothesis (i.e., 65.5% observed vs. 71.2% expected, p = 0.009) reported perceived serious treatment by ED staff, more participants <50 years than would be expected under the null hypothesis (i.e., 12.0% observed vs. 9.3% expected, p = 0.049) reported perceived dismissive treatment by ED staff, and more participants <50 years than would be expected under the null hypothesis (i.e., 13.3% observed vs. 10.8% expected, p = 0.02) reported discharge from the ED without a diagnosis. Conclusions: Results of this study highlight the different experiences of younger SCAD survivors' engaging with providers in the ED. Further research regarding strategies for increasing ED providers' clinical interrogation of SCAD when treating and evaluating younger female patients presenting with ACS symptoms is indicated.

Vascular histopathology and connective tissue ultrastructure in spontaneous coronary artery dissection: pathophysiological and clinical implications.

AIMS: Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndromes and in rare cases sudden cardiac death (SCD). Connective tissue abnormalities, coronary inflammation, increased coronary vasa vasorum (VV) density, and coronary fibromuscular dysplasia have all been implicated in the pathophysiology of SCAD but have not previously been systematically assessed. We designed a study to investigate the coronary histological and dermal collagen ultrastructural findings in SCAD. METHODS AND RESULTS: Thirty-six autopsy SCAD cases were compared with 359 SCAD survivors. Coronary and myocardial histology and immunohistochemistry were undertaken. Transmission electron microscopy (TEM) of dermal extracellular matrix (ECM) components of n = 31 SCAD survivors and n = 16 healthy volunteers were compared. Autopsy cases were more likely male (19% vs. 5%; P = 0.0004) with greater proximal left coronary involvement (56% vs. 18%; P < 0.0001) compared to SCAD survivors. N = 24 (66%) of cases showed no myocardial infarction on macro- or microscopic examination consistent with arrhythmogenic death. There was significantly (P < 0.001) higher inflammation in cases with delayed-onset death vs. sudden death and significantly more inflammation surrounding the dissected vs. non-dissected vessel segments. N = 17 (47%) cases showed limited intimal fibro-elastic thickening but no features of fibromuscular dysplasia and no endothelial or internal elastic lamina abnormalities. There were no differences in VV density between SCAD and control cases. TEM revealed no general ultrastructural differences in ECM components or markers of fibroblast metabolic activity. CONCLUSIONS: Assessment of SCD requires careful exclusion of SCAD, particularly in cases without myocardial necrosis. Peri-coronary inflammation in SCAD is distinct from vasculitides and likely a reaction to, rather than a cause for SCAD. Coronary fibromuscular dysplasia or increased VV density does not appear pathophysiologically important. Dermal connective tissue changes are not common in SCAD survivors.

Pregnancy-Related Aortic Complications in Women With Marfan Syndrome.

BACKGROUND: The risk of pregnancy-associated vascular complications in Marfan syndrome (MFS) is uncertain because of ascertainment bias, prepartum lack of knowledge of diagnosis, and insufficient peripartum imaging data. Furthermore, U.S. and European guidelines differ in pregnancy recommendations in MFS. OBJECTIVES: This study describes a single-center experience of 169 MFS women to address these gaps. METHODS: Clinical, imaging, and pregnancy history were compared in never vs ever-pregnant MFS women, and pregnancy-associated vascular complications were described. RESULTS: A total of 74 ever-pregnant women had 112 live births. Elective aortic root replacement occurred at a younger age in never-pregnant women (33 years vs 42 years; P = 0.0026). Although aortic dissection prevalence did not differ between never-pregnant vs ever-pregnant women (23% vs 31%; P = 0.25), it tended to occur at an earlier age in the former group (38 years vs 45 years; P = 0.07). Of observed "sanctioned" pregnancies with prepartum diameters ≤4.5 cm, mean pregnancy-related aortic diameters remained stable. In total, 5 dissections were associated with pregnancy: 2 type A in women unaware of their diagnosis; and 2 type B and 1 isolated coronary artery dissection in women aware of their diagnosis. Dissection rates were 5-fold higher in the pregnancy vs nonpregnancy period. CONCLUSIONS: Pregnancy-related type A dissection only occurred in patients unaware of their diagnosis. Type B dissection remains an unpredictable complication. Although there were baseline differences between the never- and ever-pregnant groups, no difference in dissection risk was observed outside the peripartum period. Those with prepartum aortic diameters between 4.0 and 4.5 cm demonstrated stable aortic dimensions throughout pregnancy. These findings provide a rationale to update existing U.S. guidelines for the management of pregnancy in MFS.

Anatomic features in SCAD assessed by CCT: A propensity score matching case control study.

PURPOSE: Spontaneous coronary artery dissection (SCAD) may occur in middle age population without any cardiovascular risk factor. We retrospectively evaluated anatomic features of 11 patients with SCAD using a coronary arteries computed tomography (CCT), compared to age and sex balanced patients who underwent CCT. MATERIAL AND METHODS: CCT was performed in 11 patients (7 females and 4 males) as follow-up in patients with SCAD (left anterior descending - LAD or circumflex artery - Cx) and compared, using the propensity score matching analysis, with 11 healthy patients. Several anatomic features were evaluated: Left main (LM) length, angle between descending coronary artery (LAD) and its first branch, angle between LAD and LM, distance from the annulus to RCA (a-RCA distance) and LM (a-LM distance) ostia and their ratio; ratio between LM length and length a-LM and tortuosity score of the vessel with SCAD. A fluid dynamic analysis has been performed to evaluate the effects on shear stress of vessels wall. RESULTS: LM length was significantly shorter in patients with SCAD versus healthy subjects (P=0.01) as well as LM length/a-LM (P=0.03) and the angle between LAD and the first adjacent branch was sharper (P<0.01). Tortuosity score showed a statistically significant difference between groups (P<0.001). Fluid dynamic analysis demonstrates that, in SCAD group, an angle<90 degree is present at the first bifurcation and it can be a cause of increased strain on vessel wall in patients with high tortuosity of coronary artery. CONCLUSION: Tortuosity and angle between the LAD and the adjacent arterial branch combined may determine increased shear stress on the vessel wall that increases the risk of SCAD.

Differential miRNAs in acute spontaneous coronary artery dissection: Pathophysiological insights from a potential biomarker.

BACKGROUND: Spontaneous Coronary Artery Dissection (SCAD) is an important cause of acute coronary syndromes, particularly in young to middle-aged women. Differentiating acute SCAD from coronary atherothrombosis remains a major clinical challenge. METHODS: A case-control study was used to explore the usefulness of circulating miRNAs to discriminate both clinical entities. The profile of miRNAs was evaluated using an unbiased human RT-PCR platform and confirmed using individual primers. miRNAs were evaluated in plasma samples from acute SCAD and atherothrombotic acute myocardial infarction (AT-AMI) from two independent cohorts; discovery cohort (SCAD n = 15, AT-AMI n = 15), and validation cohort (SCAD n = 11, AT-AMI n = 41) with 9 healthy control subjects. Plasma levels of IL-8, TGFB1, TGBR1, Endothelin-1 and MMP2 were analysed by ELISA assays. FINDINGS: From 15 differentially expressed miRNAs detected in cohort 1, we confirmed in cohort 2 the differential expression of 4 miRNAs: miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p, whose expression was higher in SCAD compared to AT-AMI. The combined expression of these 4 miRNAs showed the best predictive value to distinguish between both entities (AUC: 0.879, 95% CI 0.72-1.0) compared to individual miRNAs. Functional profiling of target genes identified an association with blood vessel biology, TGF-beta pathway and cytoskeletal traction force. ELISA assays showed high plasma levels of IL-8, TGFB1, TGFBR1, Endothelin-1 and MMP2 in SCAD patients compared to AT-AMI. INTERPRETATION: We present a novel signature of plasma miRNAs in patients with SCAD. miR-let-7f-5p, miR-146a-5p, miR-151a-3p and miR-223-5p discriminate SCAD from AT-AMI patients and also shed light on the pathological mechanisms underlying this condition. FUNDING: Spanish Ministry of Economy and Competitiveness (MINECO): Plan Nacional de Salud SAF2017-82886-R, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundación BBVA a equipos de Investigación Científica 2018 and from Caixa Banking Foundation under the project code HR17-00016 to F.S.M. Instituto de Salud Carlos III (AES 2019): PI19/00565 to F.R, PI19/00545 to P.M. CAM (S2017/BMD-3671-INFLAMUNE-CM) from Comunidad de Madrid to FSM and PM. The UK SCAD study was supported by BeatSCAD, the British Heart Foundation (BHF) PG/13/96/30608 the NIHR rare disease translational collaboration and the Leicester NIHR Biomedical Research Centre.

Disección coronaria espontánea asociada a lupus eritematoso sistémico / Spontaneous coronary dissection associated with systemic lupus erythematosus

Resumen A 29 year old female with a past medical history of systemic lupus erythematosus, diagnosed 15 years earlier, presents with lupus nephritis, currently on peritoneal dialysis. She had myopericarditis in 2012 and is currently on immunosuppressants. The patient began with exertional dyspnea and angina 2 weeks before admission. An echocardiogram was performed, reporting severe mitral and tricuspid insufficiency. Afterwards, the patient presented with resting angina associated with an adrenergic and vagal response. Initially, rheumatology ruled out autoimmune activity caused by lupus. We performed a coronary angiogram based on clinical presentation, EKG changes and biomarkers, finding a trivascular coronary artery disease classified as a Markis I coronary artery ectasia and a coronary dissection of the ramus intermedius and the circumflex, posterior to the first obtuse marginal artery. Cardiothoracic surgery considered intervention with a coronary bridge posterior to the dissection of the intermedius ramus artery, marginal obtuse and posterolateral artery, as well as a mitral valve replacement and a tricuspid valve repair. Coronary dissection is more common in women (70%), clinical presentation varies from unstable angina to sudden death. In lupus nephritis, it is an uncommon form of extra renal vasculitis. Treatment depends on the number of arteries affected, as well as the haemodynamic state of the patient. It is imperative to individualize treatment options.

Abstract Se presenta el caso de una paciente de 29 años con antecedente de lupus eritematoso sistémico diagnosticado 15 años antes, que desarrolló nefropatía lúpica actualmente en diálisis peritoneal, cuadro de miopericarditis en 2012 y bajo tratamiento inmunosupresor. Inició con deterioro de su clase funcional por disnea y angina 2 semanas previas al ingreso. Se le realizó ecocardiograma, el cual reportó insuficiencias mitral y tricuspídea graves. Posteriormente presentó angina en reposo asociada a descarga adrenérgica y vagal. A su ingreso se descarta actividad lúpica por reumatología. Por presentación clínica, cambios en electrocardiograma y biomarcadores, se realizó cateterismo cardiaco, que reportó enfermedad coronaria trivascular con ectasia coronaria Markis I y disección coronaria de ramo intermedio y circunfleja posterior a la primera marginal obtusa. Se consideró por el servicio de cirugía cardiotorácica realizar intervención con puente coronario posterior a disección del ramo intermedio, marginal obtusa y posterolateral, así como cambio valvular mitral y plastia tricuspídea. La disección coronaria espontánea es más frecuente en las mujeres (70%); puede presentarse como angina inestable y hasta como muerte súbita. La asociación con lupus eritematoso sistémico es poco frecuente, con una incidencia del 0.42%. En la nefropatía lúpica es una manifestación poco frecuente de vasculitis extrarrenal. El tratamiento de elección depende del número de vasos afectados y del estado hemodinámico, por lo que es necesario individualizarlo para cada paciente.

Spontaneous coronary artery dissection in association with cabergoline therapy.

Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognised cause of acute coronary syndrome. While numerous risk factors are associated with SCAD, one potential cause is coronary artery vasospasm. The use of cabergoline-an ergot derivative and dopamine agonist that may induce vasospasm-has been associated with SCAD in one other case report worldwide. Here, we describe SCAD in a 37-year-old woman on long-term cabergoline therapy with no other cardiac risk factors. Cabergoline-induced SCAD should be considered in patients presenting with an acute coronary syndrome who are treated with this medication.

A rare case of fibromuscular dysplasia involving multiple vascular beds.

OBJECTIVE: Fibromuscular dysplasia rarely involves vessels other than the renal and carotid arteries. We present a case of a rare fibromuscular dysplasia involving multiple vascular beds in a young female patient with history of spontaneous coronary artery (SCAD). METHODS: This is a case report with review of the literature using PubMed search for other cases of fibromuscular dysplasia that involves multiple vascular beds and its association with SCAD. The patient agreed to publish her case including her images. RESULTS: Fibromuscular dysplasia involving multiple vascular beds in a young female patient with prior coronary dissection is rarely reported in the literature. CONCLUSION: Fibromuscular dysplasia affecting multiple vascular beds is rare but should be suspected in patients with SCAD, particularly young female patients.

Spontaneous Coronary Artery Dissection in Relation to Physical and Emotional Stress: A Retrospective Study in 4 Arab Gulf Countries.

Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome and sudden cardiac death. The triggers for SCAD often do not include traditional atherosclerotic risk factors. The most commonly reported triggers are extreme physical or emotional stress. The current study compared in-hospital and follow-up events in patients with SCAD with and without reported stress. Data from 83 patients with a confirmed diagnosis of SCAD were collected retrospectively from 30 centers in 4 Arab Gulf countries (KSA, UAE, Kuwait, and Bahrain) from January 2011 to December 2017. In-hospital myocardial infarction (MI), percutaneous coronary intervention (PCI), ventricular tachycardia/ventricular fibrillation, cardiogenic shock, death, ICD placement, dissection extension) and follow-up (MI, de novo SCAD, death, spontaneous superior mesenteric artery dissection) events were compared between those with and without reported stress. Emotional and physical stress was defined as new or unusually intense stress, within 1 week of their initial hospitalization. The median age of patients in the study was 44 (37-55) years. Foty-two (51%) were women. Stress (emotional, physical, and combined) was reported in 49 (59%) of all patients. Sixty-two percent of women with SCAD reported stress, and 51 % of men with SCAD reported stress. Men more commonly reported physical and combined stress. Women more commonly reported emotional stress (P < 0.001). The presence or absence of reported stress did not impact on overall adverse cardiovascular events (P = 0.8). In-hospital and follow-up events were comparable in patients with SCAD in the presence or absence of reported stress as a trigger.

Three-dimensional geometry of coronary arteries after arterial switch operation for transposition of the great arteries and late coronary events.

OBJECTIVE: Using 3-dimensional (3D) modeling to predict late coronary events after the arterial switch operation (ASO) for transposition of the great arteries (TGA). METHOD: We reviewed 100 coronary computed tomography scans performed after ASO randomly selected from free-from-coronary-event patients and 21 coronary computed tomography scans from patients who had a coronary event later than 3 years after ASO. Using 3D modeling software, we defined and measured 6 geometric criteria for each coronary artery: Clockwise position of coronary ostium, First centimeter angle defined as the angle between of the coronary artery ostium and the first centimeter of the vessel, Minimal 3D angle between the coronary first centimeter and the aortic wall, ostium height defined as the distance between the ostium and the aortic valve, distance between the coronary ostium and the pulmonary artery, and distance between the coronary first centimeter and the pulmonary artery. RESULTS: None of the right ostium geometric parameters were associated with coronary events. Four out of 6 criteria of left coronary artery geometry were associated to coronary events: Clockwise position of the left ostium >67° (P < .001), First centimeter angle >62° (P < .01), minimal 3D angle <39° (P = .003), distance between the coronary ostium and the pulmonary artery <1 mm/mm (P = .03). The association of first centimeter angle >62° and minimal angle in 3D <39° had a 88% sensitivity and a 81% specificity to predict coronary events (receiver operator characteristics curve, 0.847; 95% confidence interval, 0.745-0.949; P < .001). CONCLUSIONS: The acquired geometric characteristics of the transferred left coronary artery are associated with coronary events. Imaging coronary arteries after ASO might be useful to select patients at higher risk of coronary events and to tailor surveillance.

Spontaneous Coronary Artery Dissection and Fibromuscular Dysplasia: Vasculopathies With a Predilection for Women.

The burden of cardiovascular disease in women is being increasingly appreciated. Nevertheless, both clinicians and the general public are largely unaware that cardiovascular disease is the leading cause of death worldwide in women in all countries and that outcomes after a heart attack are worse for women than men. Of note, certain types of cardiovascular disease have a predilection for women, including spontaneous coronary artery dissection (SCAD) and fibromuscular dysplasia (FMD). Although uncommon, SCAD is being increasingly recognised as the cause of an acute coronary syndrome (ACS) and can recur. It is a potentially fatal, under-diagnosed condition that affects relatively young women, who often have few traditional risk factors, and is the commonest cause of a myocardial infarction associated with pregnancy. In contrast, FMD often remains silent but when manifested can also cause major sequelae, including renal infarction, stroke, cervical artery dissection and gut infarction. Here we provide an update on the diagnosis, aetiology and management of these important disorders that overwhelmingly affect women.

Spontaneous coronary artery dissection: presentation and management options.

Coronary artery dissection is a serious, life-threatening heart condition. It can occur spontaneously or due to traumatic or iatrogenic causes. Spontaneous coronary artery dissection (SCAD) is often misdiagnosed as most patients present with symptoms resembling those of an acute coronary syndrome. Clinical sequelae of SCAD include debilitating morbidities such as myocardial infarction, myocardial ischaemia, sudden cardiac death, ventricular arrhythmias amongst many other myocardial ischaemia associated complications. There are two main methods of managing patients with SCAD; conservative management with medical therapy or revascularisation by percutaneous coronary intervention or coronary artery bypass grafting.

The shearing stress of baseball-spontaneous coronary artery dissection in a male athlete.

The following is a case report of an atypical presentation of spontaneous coronary artery disease. In this case, a male with risk factors, precipitated by an emotional stress, presented to the emergency room with atypical chest pain. Cardiac catheterization revealed tapering of the mid-left anterior descending artery, consistent with non-atherosclerotic spontaneous coronary artery disease. However due to repeat chest pain, a repeat cardiac catheterization was performed, revealing 100% occlusion of the mid-LAD. This case represents an atypical presentation of a pathology that is frequently missed, and underreported. This is important to discuss in order to increase awareness, as the management and follow up are actually conservative.

COVID-19: A double threat to takotsubo cardiomyopathy and spontaneous coronary artery dissection?

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that has affected millions of individuals worldwide. Prior studies suggest that COVID-19 may be associated with an increased risk for various cardiovascular disorders, such as myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism. Early reports of non-COVID-19 patients have described the concurrence of takotsubo cardiomyopathy (TTC) and spontaneous coronary artery dissection (SCAD). However, the interplay between COVID-19, TTC and SCAD has not been well established. We herein propose two sets of two-hit hypotheses for the development of SCAD and TTC in the context of COVID-19. The first two-hit hypothesis explains the development of SCAD, in which TTC-associated formation of vulnerable coronary substrate serves as the first hit (predisposing factor), and COVID-19-associated inflammation and vascular disruption serves as the second hit (precipitating factor). The second two-hit hypothesis is proposed to explain the development of TTC, in which SCAD-associated formation of vulnerable myocardial substrate serves as the first hit, and COVID-19-associated sympathetic overactivity serves as the second hit. Under this conceptual framework, COVID-19 poses a double threat for the development of SCAD (among patients with underlying TTC) as well as TTC (among patients with underlying SCAD), thereby forming a reciprocal causation. This hypothesis provides a rationale for the joint assessment of TTC and SCAD in COVID-19 patients with pertinent cardiovascular manifestations.