Not So Benign Chest Pain in the Young: A Story of Spontaneous Coronary Artery Dissection and Fibromuscular Dysplasia

Abstract

Spontaneous coronary artery dissection (SCAD) is a rare clinical entity, often presenting similar to atherosclerotic acute coronary syndrome (ACS), although it is a non-atherosclerotic, non-traumatic, and non-iatrogenic coronary artery pathology. We report the case of a 36-year-old woman who presented with substernal, pressure-like chest pain without aggravating, alleviating, or associated symptoms. Initial evaluation revealed elevated troponin levels which peaked at 8.71 ng/mL. Electrocardiogram showed borderline J point elevation in the lateral leads. A transthoracic echocardiography revealed mild left ventricular dysfunction with an estimated ejection fraction of 45% to 50%, an akinetic apex with hyperdynamic basal segments, suggestive of stress cardiomyopathy. However, a left anterior descending artery (LAD) infarction could not be excluded. Emergent coronary angiography revealed SCAD of the LAD. No coronary interventions were performed. The patient was managed medically with dual antiplatelet therapy and beta-blockers. Given the high suspicion for fibromuscular dysplasia (FMD), computed tomographic angiography (CTA) of the head to pelvis was performed. The CTA neck showed bilateral focal areas of mild stenosis and dilation of the distal cervical internal carotid artery, and CTA abdomen revealed multiple splenic artery aneurysms, diagnostic of FMD. Unlike atherosclerotic ACS, our patient was managed medically without percutaneous intervention. This case illustrates the rare occurrence of myocardial injury due to SCAD which results in spontaneous intramural hematoma formation rather than atherosclerotic plaque rupture typically seen in ACS. FMD remains the most commonly associated condition with SCAD.

Introduction

Spontaneous coronary artery dissection (SCAD) is a rare clinical entity that presents similar to other causes of acute coronary syndrome (ACS). Despite the similarities in the clinical presentation of SCAD and atherosclerotic ACS, these are 2 distinct entities with very different epidemiology, risk factors, pathophysiology, management, and associations. Despite advances in imaging and the development of SCAD angiographic classifications, SCAD continues to be overlooked and managed similar to highly prevalent atherosclerotic ACS, mostly due to the lack of evidence regarding specific treatment modalities. We present a rare case of a 36-year-old woman presenting with chest pain, found to have SCAD as the culprit lesion in the setting of fibromuscular dysplasia (FMD).

Case Presentation

A 36-year-old woman with a history of preeclampsia during her first pregnancy presented to the emergency department with chest pain. She reported a substernal, pressure-like chest pain that began early in the morning while driving, radiating to the neck, rated an 8 out of 10 in intensity, lasting 40 minutes, without any aggravating, relieving factors, or associated symptoms such as diaphoresis, dyspnea, or nausea. She experienced a similar episode the previous night while in bed that lasted for 3 to 4 hours. She denied any trauma, headache, dizziness, cough, fever, abdominal, or back pain. She reported no smoking, alcohol or drug use, family history of cardiac disease, psychiatric disorders, postpartum cardiomyopathy, or current stressors. Her last pregnancy was approximately 5 years ago. By the time of admission, the patient’s chest pain had resolved.

On evaluation, the patient was vitally stable, had an unremarkable physical examination, and laboratory investigations showed normocytic anemia with a hemoglobin of 11.3 (normal 12-16 g/dL), and an elevated initial troponin level of 0.43 (normal <0.034 ng/mL), which trended up and peaked at 8.71 ng/mL. Electrocardiogram showed borderline J point elevations in lateral leads (Figure 1). Transthoracic echocardiogram showed an estimated ejection fraction of 45% to 50%, an akinetic apex with hyperdynamic basal segments, suggestive of stress (Takotsubo) cardiomyopathy. Given these findings, left anterior descending artery (LAD) infarction could not be ruled out. Despite her low pretest probability for atherosclerotic disease, coronary artery disease involving the LAD territory and stress cardiomyopathy remained the main differential diagnoses.

Figure 1.

Patient’s initial 12-lead EKG: Normal sinus rhythm with sinus arrhythmia, rightward axis, QR and RSR’ patterns in V1 and V2 suggest but do not meet criteria for right ventricular conduction delay given a normal QRS duration (96 ms). There is also borderline J point elevation (0.5 mm) in lateral leads.

The patient underwent emergent coronary angiography which revealed SCAD of the LAD (Figure 2). There was no limiting flow in the LAD or other significant obstructive coronary artery disease. Left ventriculography showed apical akinesis with basal hyperkinesis during systole, consistent with Takotsubo cardiomyopathy. As no flow-limiting LAD occlusion was seen, no percutaneous coronary intervention (PCI) was performed. The patient was managed medically with dual antiplatelet therapy (aspirin and clopidogrel) and metoprolol. Given the finding of SCAD, FMD was a significant differential diagnosis for the underlying pathology. Hence, further workup with computed tomographic angiography (CTA) from the head to pelvis was done. The CTA neck showed a bilateral focal area of mild stenosis and dilation involving the distal cervical internal carotid artery (ICA) (Figure 3). In addition, CTA of the abdomen and pelvis also showed multiple splenic artery aneurysms, with the most proximal measuring up to 1.9 cm. These findings were consistent with a diagnosis of FMD, which predisposed our patient to developing SCAD. On further questioning, the patient was unable to report any known family history of arteriopathies, including aneurysms, dissections, strokes, myocardial infarctions, sudden cardiac death, or diagnosed FMD, to the best of her knowledge.

Figure 2.

Coronary angiogram (I-II) showing spontaneous coronary artery dissection (SCAD) involving the left anterior descending artery (LAD) depicted as the long and smooth narrowing of the LAD segment between a and b—type 2 SCAD. The left ventriculography (III-IV) shows the heart during diastole (III) and at systole (IV) with apical akinesis and basal hyperkinesis depicting the classic apical ballooning/mid-ventricular ballooning of stress cardiomyopathy.

Figure 3.

Computed tomographic angiogram (CTA) of the neck (A) showing bilateral focal area of mild stenosis and dilation involving distal cervical internal carotid artery (gray arrows).

Discussion

Spontaneous coronary artery dissection is defined as a non-atherosclerotic, non-traumatic, and non-iatrogenic coronary artery dissection. ¹ First described by Pretty et al as a rare and fatal cause of ACS in young women, advances in intravascular imaging have improved our understanding of the disease and hinted at higher prevalence than previously assumed.^2-4 Accurate prevalence of the disease has not been established but Nishiguchi et al have shown up to 4% of ACS cases to be due to SCAD, commonly affecting young women, less than 50 years old, without typical risk factors such as smoking and dyslipidemia. ⁴ Young age, female sex, and lack of risk factors, as seen in our case, do not paint a grave clinical picture for ACS, often delaying diagnosis. Electrocardiogram findings were not very remarkable in our patient, and the echocardiogram showing akinetic apical segments was concerning for stress cardiomyopathy. Stress cardiomyopathy being a diagnosis of exclusion, coronary angiogram is necessary prior to establishing the diagnosis. The increasing troponin levels in a young woman without any risk factors also made SCAD a top differential. High clinical suspicion and awareness of this critical differential for chest pain in a young population are essential for timely management.

Myocardial injury in SCAD results from artery obstruction due to spontaneous intramural hematoma (IMH) formation within the wall that compresses the true lumen rather than atherosclerotic plaque rupture. ⁵ Intimal tear leading to a false lumen or spontaneous hemorrhage from vasa vasorum is commonly accepted mechanisms for the IMH.^6,7 While intracoronary imaging is ideal to confirm the diagnosis, coronary angiography should be undertaken as soon as possible. Three types of dissections are outlined by the Saw angiographic SCAD classification: type 1, multiple radiolucent lumens; type 2, diffuse stenosis of varying severity and length; type 3, focal stenosis similar to atherosclerosis. ⁸ Our patient was taken for immediate angiography which showed LAD dissection, the most commonly affected artery, consistent with type 2. ⁹

Unlike atherosclerotic ACS management, PCI has been shown to increase the risk of complications in SCAD. ¹⁰ Weaker artery walls may predispose to further extension of the false lumen with balloon inflation or stent placement. The IMH may also be absorbed over time, predisposing a stent malapposition and in turn increasing the risk of stent thrombosis. Currently, no guidelines exist dictating intervention, but expert opinion recommends approaches such as placing long drug-eluting stents covering in excess of 5 to 10 mm on both edges of IMH, direct stenting without balloon predilation, and balloon angioplasty alone to restore coronary flow without stenting. ¹¹ Given the increased risks with stent placement, our patient was managed conservatively without stent placement. Guidelines for medical management following PCI have not been well established but some experts recommend aspirin and clopidogrel for 1 year similar to other ACS. ¹² Our patient was discharged on these medications as well despite not having a stent.

Fibromuscular dysplasia is one of the most commonly associated conditions with SCAD. Multifocal FMD is a non-atherosclerotic and non-inflammatory arteriopathy involving multiple arterial beds, characterized by alternating constriction and dilation of affected arteries in a string-of-beads appearance resulting in tortuosity, stenosis, aneurysm, and dissection. ¹³ Our patient was noted to have focal areas of mild stenosis and dilation involving distal cervical ICA (Figure 3) as well as multiple splenic artery aneurysms on CTA of the neck and abdomen, respectively, confirming the diagnosis of FMD. While the pathogenesis of FMD is not fully understood, a genetic predisposition has been elucidated as playing a major role.^14-16 A complex interplay of a combination of gene loci and variants rather than a single gene involvement seems to be favored. Genetic variants in the phosphatase and actin regulator 1 gene (PHACTR1) and the collagen type V alpha-1 gene (COL5A1) are just 2 examples that have been shown to be associated with multifocal FMD, arterial dissections, and aneurysms, underpinning the pathophysiologic link between FMD and cardiovascular disease.^15,16 Patients with FMD need a comprehensive evaluation and close monitoring for potential dysplasia-associated arterial disease, especially if the symptomology is suggestive. Medical management with close outpatient observation is preferred in patients who develop SCAD, as was the case with our patient.

Given the genetic predisposition and familial risk of FMD, an assessment of at-risk family members of patients with FMD is very important for early detection and management. However, thresholds for genetic testing, screening, or monitoring have not been well established. The consensus favors screening patients with FMD as well as their first- and second-degree relatives who are symptomatic or have a suggestive history and/or physical examination for an underlying arteriopathy, using Duplex ultrasonography or head to pelvis CTA.^17,18 Routine genetic testing in patients with FMD or their family members, even following a SCAD, has a low yield and is not currently recommended.^19,20 Hopefully, as ongoing genetic advances in medicine continue to evolve with promise, clearer thresholds for disease assessment in families will be established.

Conclusion

Spontaneous coronary artery dissection is an independent entity that is more common than previously imagined, especially in this age of sophisticated angiographic imaging. While young women are less likely to be affected by atherosclerotic ACS, SCAD remains an important and often underdiagnosed differential for chest pain in such patients. Even though it is a rare condition, SCAD should always be a differential diagnosis considered in patients with ACS who have a low pretest probability for atherosclerotic CAD, especially pregnant or young women of reproductive age. Given the increased risks with stent placement in SCAD patients, medical management with dual antiplatelet therapy for at least 1 year, similar to other ACS, is recommended. While this case is not an unusual observation, it highlights the association between FMD and SCAD, a potentially fatal cause of ACS in young women. An understanding of the disease spectrum, its pathogenesis, genetic associations, and clinical implications, is vital for the timely and comprehensive assessment and management of these patients and their families.