Beyond the Norm: Decoding Spontaneous Coronary Artery Dissection as an Unusual Cause of Acute Coronary Syndrome

Abstract

Description

Spontaneous coronary artery dissection (SCAD) is a rare nonatherosclerotic cause of myocardial infarction among young women, particularly during pregnancy. As the name suggests, SCAD is caused by the spontaneous formation of the false lumen within the coronary artery wall, thus compromising the blood flow to the myocardium. Unlike atherosclerotic acute coronary syndromes, SCAD is not directly associated with diabetes or hypertension; moreover, underlying connective tissue defects and inflammation are considered more contributory towards its etiology. Although its pathophysiology is not well understood, multiple theories have been proposed. Clinically, SCAD has a similar presentation to acute coronary syndromes, including substernal chest pain, elevated cardiac enzymes, ST-segment elevation myocardial infarction, and T wave changes on the ECG. Due to its elusive etiology, variable clinical presentation, and potential for catastrophic outcomes, it is essential to make a proper diagnosis using tools such as coronary angiography, optical coherence tomographic imaging, intravascular ultrasound, and cardiac magnetic resonance imaging. In this article, we review the current understanding of SCAD, encompassing its epidemiology, pathophysiology, clinical presentation, and diagnostic and management options.

Introduction

Spontaneous coronary artery dissection (SCAD) is an infrequent yet emerging cause of nonatherosclerotic acute coronary syndrome (ACS) and sudden cardiac death primarily affecting young women. Spontaneous coronary artery dissection is typically characterized by the spontaneous formation of false lumen within the coronary artery wall, which may potentially impede normal blood flow due to the external compression of the true lumen.¹ The majority of SCAD cases are observed in women, with recent research indicating that they make up 87% to 95% of cases, with an average age of onset ranging from 44 to 53 years. While the majority of patients in extensive studies have been of white descent, a more diverse population-based cohort, consisting of 45% Hispanic Americans and 16% Black individuals, demonstrated similar presentation and outcomes across these different populations.² Although the American Heart Association recently stated that a recurrence of SCAD is identified when a minimum of 30 days pass between the initial occurrence of SCAD and any subsequent instances, the concept of recurrent SCAD lacks a uniform definition across various studies. Recurrent SCAD is thought to occur between 10% and 15% of the time in the most recent cohorts.³

The exact mechanisms causing the pathophysiology of SCAD are still only partially understood. The crux of this phenomenon, according to a widely accepted theory, is the confluence of defects in connective tissue and inflammation (Figure 1).⁴ It’s interesting to note that the traditional risk factors for cardiovascular disease, such as diabetes and hypertension, have only sporadic relationships with SCAD. There may be connections between SCAD and a variety of issues, according to extensive research. It may be triggered by intense emotional stress, physical stress, such as strenuous exercise, labor, delivery, and the Valsalva maneuver, or recreational drugs, such as cocaine and amphetamines in the presence of underlying predisposing factors, such as fibromuscular dysplasia (FMD), connective tissue disorders, including Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome type 4, cystic medial necrosis, alpha-1 antitrypsin deficiency, polycystic kidney disease, systemic inflammatory disease, including systemic lupus erythematosus, inflammatory bowel disease, celiac disease, vasculitis associated diseases, sarcoidosis, rheumatoid arthritis, pregnancy, and hormonal therapy, including oral contraceptives.⁵ The most frequent manifestations involve the abrupt onset of chest pain accompanied by syncope, which is often coupled with an increase in cardiac enzymes and ST-segment elevation myocardial infarction on ECG similar to atherosclerotic ACS. Other fatal presentations include sustained or nonsustained ventricular arrhythmias and sudden cardiac death.⁶

Figure 1.

A flowchart shows possible pathways that lead to spontaneous coronary artery dissection.

Differentiating ACS caused by SCAD from the more common atherosclerotic causes is extremely important due to variations in their treatment approaches. This differentiation is particularly challenging in emergencies, making invasive coronary angiography the primary choice for initial imaging. While specific diagnostic tools, like intracoronary imaging methods, such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS), can enhance and confirm the diagnosis, some are cautious about using these techniques due to the potential risk of worsening the dissection.⁴ Currently, there are no established guidelines that must be adhered to when managing cases of SCAD. The objective of this narrative review is to address gaps in knowledge regarding the pathophysiological mechanisms underlying SCAD and to resolve disparities in the selection of diagnostic methods. Additionally, this article intends to assist clinicians in developing individualized management strategies for each patient.

Pathophysiology

Spontaneous coronary artery dissection is defined as a nonatherosclerotic coronary artery disease, characterized by the development of a false lumen within the coronary artery wall, forming an intramural hematoma that compresses the true lumen.⁷ Based on morphology, SCAD can be differentiated into 2 types, fenestrated and nonfenestrated SCAD. In fenestrated SCAD, there is a continuity present between the true lumen and the false lumen. Meanwhile, in nonfenestrated, there’s no continuity whatsoever.⁸ There are 2 theories that have been proposed for the development of intramural hematoma. According to the first theory, a microvascular rupture in the arterial wall leads to the formation of an expanding intramural hematoma and subsequent pressurization and external compression of true lumen, resulting in myocardial infarction. In some cases, the pressure differential may exceed the intimal yield stress leading to a rupture in the intima-medial membrane, creating a fenestration and equalization of pressure between true and the false lumens.⁹ The second theory proposes that an intimal tear is an inciting event which allows blood to enter from the true lumen to the false lumen.¹⁰ Findings from higher-resolution optic tomographic studies have provided the support for the first theory.¹¹

Spontaneous coronary artery dissection most commonly involves the left coronary artery system. The left anterior descending artery is most commonly involved with dissection, noted in 48%–57% of cases. Most histological sections reveal that the dissection plane lies between the arterial media and adventitia, or in the outer media.¹² There are uncertainties regarding the initiation of microvascular dissection and formation of an intramural hematoma. Histopathology shows an adventitial and periadventitial mixed infiltrate, often with predominance of eosinophils in the wall of coronary arteries, in many studies. Some authors consider it as a primary inciting event, while others attribute it to a nonspecific response to vascular injury.¹⁰ Pitliya et al postulated a causal relationship between inflammatory mediators released from eosinophils and SCAD. Eosinophilic degranulation releases cytotoxic substances that damage the vascular endothelium, type I and type II collagen, and elastin present in the capillary walls, leading to the capillary wall weakening.¹³ Circulating fibrillin-1, a degradation product of elastin, has been found in higher concentrations in SCAD patients as compared to non-ACS SCAD or healthy controls and is associated with poor prognosis in SCAD.¹⁴ Eosinophils have proangiogenic properties that lead to neovascularization of vasa vasorum and dilatation of intimal capillaries.¹⁰ Optical tomographic imaging studies pointed out an increased vasa vasorum density in the adventitia of the coronary arteries of convalescing patients, favoring a reactive mechanism for eosinophilic accumulation.⁹ Taek et al reported increased density of vasa vasorum in the adventitia and proposed that leakage of neoangiogenic capillaries may be linked to SCAD.¹⁵

The role of coronary arterial endothelium dysfunction as an inciting event is not well understood. Endothelial dysfunction and impaired vasomotion have been reported in the patients of SCAD in comparison to matched controls. Mori et al attributed the coronary microvascular dysfunction to underlying disorders, such as coronary FMD.¹⁶ Up to 66% of SCAD cases are associated with the presence of many extracranial vascular abnormalities, frequently involving renal, vertebral, mesenteric, and cerebral arteries.¹⁷ While FMD is most common, other isolated arteriopathies, such as aneurysms, tortuosity, and dissections, have been noted.¹⁸ Notably, coronary artery tortuosity is present in 78% of SCAD patients compared to only 17% of non-SCAD patients, and recurrent dissections tend to occur preferentially in these tortuous segments, accounting for nearly 80% of SCAD recurrences.¹⁹ Kok et al reported a higher prevalence of migraines in the patients of SCAD (42%) as compared to non-SCAD cohorts (24%).²⁰ A common genetic predisposition is seen in these disorders. Migraines, SCAD, and FMD are associated with the PHACTR1 genetic variant, while migraines and SCAD are also linked to the presence of a low-density lipoprotein receptor-related protein 1 variant. The PHACTR1 gene codes for a protein that binds to actin and is involved in cytoskeletal organization. This genetic variant may predispose to arterial frailty and be a predisposition for dissection in women and atherosclerotic changes in men.²¹ A lower association of SCAD has been reported with systemic inflammatory conditions, such as systematic lupus erythematosus, inflammatory bowel disease, polyarteritis nodosa, sarcoidosis, coeliac disease, etc. The most likely explanation for the cooccurrence is an increased susceptibility to dissection due to vessel wall inflammation and atherosclerotic changes, resulting from systemic inflammation. Various emotional and physical stressors have been implicated in the pathophysiology of SCAD. An exact mechanism is unknown, but it may be related to an increased sympathetic stimulation leading to a catecholamine surge and hemodynamic changes, resulting in a potential intimal tear or rupture of the vasa vasorum.²²

Discussion

Spontaneous coronary artery dissection can be effectively prevented and managed with a better understanding of the condition. This section addresses the presentation, diagnosis, and management of SCAD, aiming to increase physicians’ awareness and encourage them to consider it in their differential diagnosis.

Presentation and Diagnosis

Spontaneous coronary artery dissection signs and symptoms can vary significantly (Table 1). Factors, including the severity of the dissection, the specific coronary artery that is affected, and potential noncardiac symptoms, can pose challenges in diagnosing SCAD. Despite the diversity in clinical presentations, nearly all SCAD patients exhibit symptoms of ACS, including substernal anginal chest pain and elevated cardiac enzymes.¹⁰ In greater than 90% of cases, anginal chest pain is the primary presentation. Angina equivalents such as dyspnea, nausea, vomiting, and diaphoresis are also associated with SCAD. Given the resemblance of these symptoms to those of ACS, SCAD is often mistaken for other cardiac conditions, resulting in misdiagnosis.²³ SCAD can also manifest as an acute myocardial infarction and can demonstrate ischemic ST elevations and T wave abnormalities on ECG. In a sample of 1079 patients with SCAD who presented to the emergency department, the initial ECG demonstrated ST elevations in 46% of patients, T wave abnormalities in 22%, and a normal ECG in 16%.²⁴ The presentation of SCAD also differs in pregnant versus nonpregnant women, with pregnancy being associated with a more complicated and a multivessel disease pathology as compared to the nonpregnant women. Pregnancy was associated with more incidence of ST-segment elevation myocardial infarction (57% vs 36%; P =.009) and left ventricular dysfunction with EF of 35% or less (26% vs 10%; P = .007) as compared to nonpregnant SCAD patients.²⁵ Due to the nonspecific presentation of this disease process, accurate diagnosis of SCAD is crucial to ensuring appropriate management.

Table 1.

Most Common Presenting Symptoms of Spontaneous Coronary Artery Dissection¹⁰

Symptom	Frequency
Chest pain	96%
Radiation to arm	51.5%
Nausea and vomiting	24%
Diaphoresis	21%
Dyspnea	20%
Back pain	14%
Dizziness	9%
Ventral tachycardia or ventral fibrillation	7%
Fatigue	5%
Headache	<2%

Once SCAD is suspected, coronary angiography should be conducted immediately, especially if ST elevations are present on ECG. Nevertheless, the diagnosis of SCAD is not always clear when using coronary angiography. Spontaneous coronary artery dissection frequently presents with intramural hematoma, an appearance that often escapes recognition on angiography and contributes to the misdiagnosis of the condition.²⁶ If the diagnosis is unclear following coronary angiography, intravascular imaging techniques including, OCT and IVUS, can serve in confirming the diagnosis, particularly if an intramural hematoma and/or a double lumen is present.²⁷ OCT has a higher spatial resolution and adeptly identifies intramural hematomas, endothelial tears, and even fine details at the endoluminal level, such as plaque composition and tissue coverage of stent struts.^28–30 Should OCT be unavailable, IVUS may be a viable alternative. Intravascular ultrasound and its high tissue penetrance offers improved visualization of fibrous lesions and lipid collections, albeit at the cost of spatial resolution, making it blind to many of the features visible on OCT.³¹ Should these imaging modalities prove inconclusive, coronary computed tomographic angiography (CCTA) and cardiac magnetic resonance (CMR) can also be used. Coronary computed tomographic angiography is a noninvasive technique that is useful in visualizing dissection flaps, intramural hematomas, and in assessing healing.²⁷ However, its spatial resolution is relatively poor for smaller vessels. In fact, less than 15% of acute SCAD cases are correctly identified with CCTA.²⁵ Cardiac magnetic resonance can confirm the presence and location of a suspected dissected coronary artery, and, therefore, aid in the diagnosis of SCAD but has been shown to have decreased sensitivity and cannot definitively exclude the diagnosis.³²

Management

Like most pathologies, available management strategies include conservative and pharmacologic options as well as nonconservative, surgical options (Figure 2). Conservative approaches to SCAD include the use of dual antiplatelet therapy (DAPT), with aspirin and clopidogrel, beta blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin II receptor blockers (ARBs). Nonconservative approaches to SCAD include percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG).³³ However, management of SCAD might be the most controversial aspect of this condition topic simply due to the lack of studies and subanalysis, which can help differentiate the outcomes of these 2 approaches. The rationale behind conservative therapy is the same rationale used in treating ACS, in that it helps to reduce myocardial wall stress, while minimizing exposure to potential complications of invasive diagnostic and revascularization procedures in patients who are low-risk.³⁴ The strong advocacy for the use of medical therapy as compared to surgical route is based on the fact that PCI/CABG have suboptimal results in terms of patient outcomes and are associated with postsurgical complications, like the iatrogenic extension of the dissection or hematoma propagation.² Coronary artery bypass grafting is preferred over PCI if the patient has left main vessel involvement or has a multivessel disease pathology (2 or more vessels involved). Usually, patients require around 5 days of inpatient monitoring to ensure there is no recurrent SCAD, a common complication, and further management is individualized based on presentation. For instance, those with heart failure are started on guideline-directed medical therapy, which includes beta blockers, ACEIs, ARBs, angiotensin receptor-neprilysin inhibitors (ARNIs), and sodium glucose cotransporter 2 inhibitors. And, those who undergo PCI/CABG are started on appropriate poststents protocol with DAPT based on the type of stent (drug eluting vs noneluting). Although there are no randomized controlled trials available, guidelines suggest discontinuing the use of anticoagulants once the diagnosis of SCAD is established and also suggest against the use of statins as it provides no added benefit. In summary, pharmacologic management is preferred unless the patient is hemodynamically unstable, in cardiogenic shock, or has ongoing myocardial ischemia, in which surgical intervention is recommended.⁵

Figure 2.

A diagnostic framework shows ways to confirm spontaneous coronary artery dissection.

Conclusion

Spontaneous coronary artery dissection is a serious and complex condition that warrants the attention of the medical community due to its potentially fatal consequences, intricate pathophysiology, and broad clinical presentation. The clinical presentation of SCAD can differ greatly between patients, ranging from ACS symptoms, such as anginal chest pain to anginal equivalents, including dyspnea and diaphoresis. The heterogeneity of these signs and symptoms and their overlap with ACS make the diagnosis of SCAD challenging and often unsuccessful. Numerous diagnostic techniques, such as coronary angiography, OCT, IVUS, CCTA, and CMR, may be required to identify and evaluate SCAD. However, even with the utilization of these techniques, accurate diagnosis of SCAD continues to pose a challenge within the health care field. Despite advancements in our understanding of SCAD, there are still sizable gaps in our knowledge surrounding its pathophysiology. Further studies should be aimed at addressing these diagnostic and pathognomonic deficits in order to improve the management of SCAD and, ultimately, patient outcomes.

Funding Statement

This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare-affiliated entity.