Spontaneous coronary artery dissection (SCAD) was first recognized in 1931 (1) and is an uncommon but important cause of myocardial infarction (MI), particularly in young people (1). It causes less than 1% of MI in some cohorts although it is likely underdiagnosed despite recent efforts at increasing awareness (2). SCAD occurs primarily in women who may not have traditional risk factors for atherosclerotic coronary artery disease and causes 25%–30% of MI in women younger than 50 years of age, as well as 15%–20% of peripartum and pregnancy-associated MI (3–7). Its pathophysiology is incompletely understood, but it probably results from dissection of the tunica media or rupture of the vasavasorum, causing intramural hemorrhage and hematoma and resultant luminal obstruction by the dissection flap or the hematoma itself. This may result in ischemia or infarction (8, 9). Prompt diagnosis is essential, as treatment differs considerably from the more common causes of MI, and SCAD is associated with high rates of complications (2). Further, SCAD highlights a vascular system at risk of further dissection, and it is linked to other vasculopathies such as fibromuscular dysplasia (FMD) and aneurysms (10, 11). A diagnosis should prompt diagnostic imaging of other vascular territories to identify aneurysms or extra-coronary abnormalities requiring treatment and referral to a vascular specialist (12). Patients may also benefit from lifestyle counseling to decrease the risk of recurrence (12). This review will discuss the clinical manifestations and various types of SCAD, diagnostic findings, surveillance for disease in the non-coronary vasculature, pharmacologic management, genetic testing, and advice for patients, particularly for patients considering pregnancy. As SCAD may be the initial presentation of an underlying vascular disease, vascular specialists should be familiar with the rapidly evolving science of SCAD, including its epidemiology, diagnosis, treatment, and the patient counseling required in this condition.

The clinical presentation of SCAD is similar to MI caused by atherosclerotic coronary artery disease and can encompass all the signs and symptoms of the acute coronary syndrome (13, 14). In one study, 30% of patients presented after physical exertion, and half presented after emotional stress, although it is important to note that no cause of SCAD is found in many patients (14). There is also an association with increased shear stress, such as with exercise, sneezing, or cocaine use (12). Because it may present as unstable angina or even as cardiac arrest, a high index of suspicion is required to make the diagnosis, particularly as patients typically have no or few risk factors for atherosclerotic disease (15).

Compared to patients with MI caused by atherosclerosis, patients with SCAD are much more likely to be female, younger, and have fewer risk factors for atherosclerotic disease (14, 17). Almost 90% of patients are female, commonly aged 47–53 years (16, 27, 28). Further, SCAD causes 15%–20% of MI during pregnancy or the peripartum period (3, 29). The reason for this sex predilection is unclear.

SCAD is associated with pregnancy, known as P-SCAD. It affects 1.81 per 100,000 pregnancies, with 70% occurring postpartum (30), usually within the first week (30), and these patients tend to have more severe presentations (30, 31). 1/3 of P-SCAD cases occur in late pregnancy and 2/3 in the early postpartum period (16, 32), and P-SCAD accounts for <5%–17% of SCAD cases overall and 14.5%–43% of pregnancy-associated AMI (2, 14, 18, 33, 34). SCAD has also been associated with multiparity (35–37), clomiphene (35), oral contraceptives (7, 37, 38), and hormone replacement therapy (7, 37, 38). Why it presents often in the peripartum period is unclear, but it could be linked to the hemodynamic changes of pregnancy such as increased cardiac output and blood volume, and reduced systemic vascular resistance (39). It is also possible that perimenopausal/peripartum hormonal fluctuation changes the quantity of elastic fibers and collagen synthesis, as well as the mucopolysaccharide content of arterial walls (3, 18, 31, 35, 39, 40). For example, one study linked estrogen exposure to increased expression of matrix metalloproteinases (MMPs) from vascular smooth muscle cells, leading to necrosis and an unsupported vasa vasorum (41). Additionally, progesterone levels remain high during pregnancy, which can cause loss of normal corrugation of elastic fibers (42). This process could lead to increased susceptibility of rupture with increased hemodynamic stress, as occurs in pregnancy and labor (41).

SCAD is also closely linked with other vasculopathies such as fibromuscular dysplasia (FMD) and has also been described in collagen-elastic fiber disorders such as Ehlers-Danlos and Marfan syndromes (7, 43–46). There is also an inconsistent association with inflammatory disorders which are in general more common in women (12, 30, 47). Regardless of pathophysiology, mortality risk is lower with acute MI from SCAD (in the non-pregnant state) in comparison to MI associated with atherosclerosis (48). This is likely secondary to younger age and lower prevalence of atherosclerotic risk factors (48).

FMD is a noninflammatory, nonatherosclerotic vasculopathy of unclear etiology that is characterized by intima and media hyperplasia, adventitial sclerosis, and destruction of normal elastic tissue. Like SCAD, FMD also primarily affects women. Recent studies have found a significant link between the two conditions (7, 10, 39, 49), especially with concomitant migraines (28, 48). More than 50% of patients with SCAD have FMD, making it the main underlying arterial abnormality observed in SCAD (7, 14, 15, 49). As both conditions are rare, this association suggests causality (39). Because of this strong correlation, all patients with SCAD should undergo screening for FMD with a comprehensive vascular physical examination and with head-to-pelvis CTA (or magnetic resonance angiography, MRA), as finding extra-coronary involvement may affect management and inform prognosis (50). For example, aneurysms or other dissections may require additional treatment to prevent rupture or longitudinal follow up with serial imaging.

Recent advances in genetics have helped to elucidate the link FMD between SCAD. They both appear to be familial in <5% of cases with autosomal dominant inheritance (51). Some studies have revealed common single nucleotide variants, though there is still no explanation as to the sex differences in SCAD (31). The PHACTR1/EDN1 (phosphatase and actin regulator and endothelin 1) locus was the first genetic risk factor to be identified to potentially link SCAD and FMD (52). Further, loss of function of PTGIR (prostaglandin reductase) is enriched in both FMD and SCAD. These mutations seem to lead to non-atherosclerotic arterial stenosis and dissection in patients diagnosed with FMD and SCAD (53).

In this section, we enlist a stepwise format to address and recognize some of the patient facing challenges in the management of post-SCAD care. These concerns focus on rehabilitation of patients and return to functional lives. (Central Illustration, Table 2).

Currently, there is one clinical trial specifically looking at the SCAD population. It is a randomized, controlled clinical trial examining the efficacy beta blockers and antiplatelet agents. The primary completion date for the trial is 2024 (74).

SCAD is a relatively rare form of vascular disease accounting for about 1% of MI and it primarily occurs in women 30–50 years of age. Knowledge of diagnosis and treatment strategies for these patients is crucial for all vascular clinicians. Prompt diagnosis is essential, which should be done with either IVUS or OCT. Non-pregnancy associated SCAD most often occurs in the LAD, while pregnancy-associated SCAD is typically multi-vessel. It is typically treated with antiplatelet therapy and beta blockers, though there is increasing evidence that a more robust combination of post-dissection care is useful. This may include revascularization in rare cases, tailored exercise recommendations, cardiac rehabilitation, and preconception counseling for those considering pregnancy. Clinicians should also be aware of the overlap between FMD and SCAD. SCAD is often misdiagnosed, which can lead to worse outcomes for these patients. Close longitudinal follow-up is essential for patients following SCAD, especially as treatment options continue to evolve. Ongoing clinical trials should shed further light on ideal management strategies in this patient population.