Spontaneous coronary artery dissection: case report and review of literature.

Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute coronary syndrome or sudden cardiac death. SCAD has most frequently been described as presenting as an acute coronary syndrome in females during the peripartum period. It may also be associated with autoimmune and collagen vascular diseases, Marfan's syndrome, chest trauma, and intense physical exercise. The most common presentation of SCAD is the acute onset of severe chest pain associated with autonomic symptoms. This condition has a high mortality rate if not identified and treated promptly. Here, we present a case of SCAD presenting with stroke, followed by a brief review.

INTRODUCTION

Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute coronary syndrome (ACS) or sudden cardiac death. Here, we present a case of SCAD in a young man who presented with stroke, followed by a review of the literature on this rare clinical entity.

THE CASE

A 26-year-old right-handed Caucasian male presented to the emergency department with the sudden onset of weakness of the left side of the body, associated with slurring of speech and a left-sided facial droop. He denied any symptoms of chest discomfort, palpitations, shortness of breath, diaphoresis, dizziness, nausea, vomiting, seizure activity, confusion, syncope, or visual disturbance. Past history was significant for an episode of deep venous thrombosis occurring 1 year prior to the current presentation. An extensive hypercoagulable workup, including protein C and S levels, factor V Leiden, antithrombin III, homocysteine levels, and antiphospholipid and anticardiolipin antibodies, was negative. There was no history of hypertension, diabetes mellitus, or dyslipidemia. The patient had no significant family history of premature coronary artery disease, but did admit to smoking one-half pack of cigarettes per day. He was taking an aspirin daily and had no known allergies. The review of symptoms was otherwise negative.

On admission, the patient with a normal body habitus appeared apprehensive but in no acute distress. Vital signs showed a regular pulse at 81 bpm and a blood pressure of 136/70 mm Hg. Carotid impulses were normal and the jugular venous pressure was not raised. Cardiac examination revealed normal heart sounds and there were no appreciable cardiac murmurs, rubs, or gallops. Lungs were clear. Neurologic examination revealed left-sided facial weakness with mild motor weakness and diminished touch and pain sensations on the left side of his body. Left-sided deep tendon reflexes were brisk and the left Babinski sign was positive.

Hypercoagulable workup was repeated and was again negative. The urine toxicology screen was negative. Carotid Doppler studies demonstrated no significant disease. Non-contrast computed tomography of the head was negative for intracerebral hemorrhage, and MRI of brain [Figure 1] demonstrated hyperintense signal on FLAIR imaging, consistent with a recent cerebral infarction in right middle cerebral artery (MCA) territory.

Figure 1

MRI (FLAIR) showing ischemic stroke in right MCA territory

The admission ECG showed normal sinus rhythm and age indeterminate anterior and inferior wall infarcts. Serial troponin I levels drawn on admission and at an eight-hourly interval thereafter were 0.02, 0.4, and 0.31 ng/ml, respectively (normal ≤0.05 ng/ml, indeterminate 0.06-0.5 ng/ml, positive >0.5 ng/ml). A transthoracic 2D echocardiogram [Figure 2] on admission demonstrated severe regional wall motion abnormality over the apical portion of interventricular septum associated with an apical mural thrombus. No valvular dysfunction was noted.

Figure 2

2D echo showing apical mural thrombus in left ventricle

The patient was given tissue plasminogen activator (tPA) in the Emergency Department at a total dose of 0.9 mg/kg along with aspirin 325 mg orally. Unfractionated heparin was started 24 h later as per the hospital protocol. Oral metoprolol and coumadin were initiated 24 h after admission. A pharmacologic stress test with technetium-gated SPECT showed a large area of moderate to severe fixed perfusion defect at the tip of the apex extending to the distal anterior wall, distal inferior wall, and the distal interventricular septum, associated with severe regional wall motion abnormality. The ejection fraction was calculated at 46%.

Cardiac catheterization with coronary angiography was performed using a right radial artery approach. Coronary angiography showed a radiolucent linear defect suggestive of an intimal dissection involving the mid to distal segment of the left anterior descending artery with Thrombolysis in Myocardial Infarction (TIMI) grade III flow [Figure 3]. Mild left ventricular systolic dysfunction with apical wall dyskinesia and a small left ventricular aneurysm were present. The patient was maintained on medical management, including oral warfarin therapy [International Normalized Ratio (INR) maintained at 2-3], aspirin, beta-blocker, and statin, with close outpatient follow-up. He was provided advice on lifestyle modifications, including smoking cessation counseling. Follow-up coronary angiography at 6 months demonstrated a stable appearance of the coronary dissection. His medical management was continued, but warfarin was discontinued after 6 months. He remains well 10 months since his initial event.

Figure 3

Coronary angiogram showing intimal dissection flap with preserved flow in distal LAD

REVIEW

The earliest report of SCAD was published in 1931 and at that time the disease entity was referred to as “dissecting aneurysm of coronary artery.”[1] Isolated dissection of the coronary artery is a relatively uncommon condition that usually presents as an ACS or sudden cardiac death, with a reported mortality of 80%.[2] Coronary artery dissection is termed spontaneous once secondary causes like coronary interventions, cardiac surgery, trauma, and aortic dissection have been excluded.

Forker et al. reported the first known survivor, a 56-year-old man who had a right coronary artery dissection with atherosclerotic vascular disease.[3] Claudon et al. in a seminal article reviewed 24 cases and concluded that the condition is common in young, postpartum women.[45] The reported incidence of SCAD varies from 0.1% to 1.1% by angiography.[6] Approximately 500 cases have been documented in the medical literature so far as there is a high incidence of sudden cardiac death associated with the condition.[7] The Western Denmark Heart registry reported 22 cases of SCAD out of a total of 11,175 ACS patients, and 77% of them were women.[8] The pathophysiology relates to the presence of a hematoma in the media of the coronary artery that compromises blood flow in the true lumen of the vessel. The inciting event is usually an intimal tear which allows blood entry into the media. If coronary blood flow is sufficiently compromised, the myocardium supplied by the affected artery may become ischemic or infarcted. The present article aims to review the existing literature related to the topic and provide a comprehensive review on this rare disease entity.

ETIOLOGY AND ASSOCIATIONS

SCAD has been reported most commonly in women during the peripartum period presumably due to hypertensive trauma during childbirth. The increased incidence of SCAD in pregnancy and postpartum period is thought to be due to decreased collagen production or enhanced degradation in intima and media of vessel wall in the postpartum period, increased shear stress on arterial wall due to augmented cardiac output, inherent hypercoagulability in peripartum state, and hemorrhagic disruption of vasa vasorum.[9] Progesterone in pregnancy causes increased fragmentation of reticular fibers along with decreased acid mucopolysachcharides, causing weakening of vessel wall. A comprehensive review by Koul et al. has shown that SCAD is more common in multiparous women, usually more than 30 years of age, and involves the left anterior descending artery (LAD). In most of the cases, and about one-third of the cases show multivessel coronary artery dissection.[10]

Shamloo et al. recently did a systematic analysis of all published cases and concluded thus: a) About 20% of cases were diagnosed postmortem and the rest by coronary angiogram; b) isolated single vessel involvement was the most frequent lesion; c) early intervention (either stent or bypass graft surgery) strategy had a superior outcome compared to conservative management; and d) administration of thrombolytics (before diagnosis of SCAD) resulted in worsening of condition in 60% of patients.[11]

Vessel wall weakness is an important substrate for development of spontaneous coronary artery dissection, be it in pregnant states or as a part of systemic inflammation. It may also be associated with autoimmune and collagen vascular diseases, Marfan's syndrome, Ehlers-Danlos syndrome, or intense physical exercise[12] [Table 1].[13-20] Anecdotal relationships have been reported with clonidine and cabergoline intake.[2122]

Table 1

Etiology and associations of SCAD[13–20]

Clinical presentation

The most common presentation of SCAD is the acute onset of severe chest pain associated with autonomic symptoms such as diaphoresis, palpitations, and either hyper- or hypotension. Asymptomatic cases are rare. The condition carries a high mortality if not identified and treated promptly. SCAD presenting as ischemic stroke is extremely unusual with only two cases reported in the medical literature.[1223]

Pathology and pathophysiology

The pathology of SCAD usually shows a dissection plane between the media and the adventitia of the artery due to cystic medial necrosis or hemorrhagic disruption of the vasa vasorum.[23] Cystic medial necrosis is a rare finding and usually involves focal fragmentation and loss of elastic fibers and smooth muscle cells of the media, associated with deposits of varying amount of acid mucopolysaccharides. The lesion is typically seen in the vessel wall of patients with Marfan's syndrome, systemic hypertension, and as a part of aging process.[24] The presence of an eosinophilic infiltrate in adventitia has also been described, particularly in non-atherosclerotic SCAD.[2526]

The histology of approximately 50% of dissections (both associated with peripartum state and those without) shows a predominant eosinophilic infiltrate. The presence of eosinophils has been thought of as a secondary reactive phenomenon rather than a primary etiological association. However, the tissue damaging effects of eosinophil granule components along with their presence in the vessel wall have been used to explain the potential role of eosinophils in the dissection process. Eosinophil granules contain collagenase, acid phosphatase, major basic protein, arylsulfatase, and beta-glucoronidase, which can significantly damage the collagen fibers of the vessel wall and possibly initiate a dissection process. In fact, SCAD has been reported in cases with Churg-Strauss syndrome,[27] drug-induced eosinophilia,[28] and in a case with peripheral eosinophilia. There is an anecdotal report where patient was treated with immunosuppressants like prednisone and cytoxan to counter the eosinophil-mediated periadventitial inflammation with favorable results.[29]

Prognosis

Dissection of the left main coronary artery or multivessel dissection carries a particularly poor prognosis.[30-34] Atherosclerotic etiology and male gender has comparatively better prognosis in this condition.[35] Recurrent coronary dissection has been reported in 50% of patients mostly within 1 or 2 months. Recurrent SCAD in subsequent pregnancies has not been reported yet.[36]

Management

The diagnosis is usually confirmed by coronary angiography. Common angiographic findings include intimal flap, two separate communicating lumens, multiple dissecting lines, and coronary aneurysm communicating with the lumen. Nitroglycerin-resistant segmental narrowing in a young female without any cardiac risks can be a presumptive diagnosis for SCAD.[3738] LAD involvement is more common in females, whereas right coronary artery (RCA) involvement is more common in males. Dissection of left main is rare.[39]

In cases requiring percutaneous coronary intervention (PCI), coronary dissection presents a unique challenge as it may prove difficult to identify the true arterial lumen and secure proper guidewire placement. Precise localization of the site and extent of dissection and identification of the true lumen may require intravascular imaging modalities such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT). IVUS has been used to visualize surface morphology, plaque architecture, and lumen size during stent implantation. The image resolution of IVUS is 100-150 μm, hence it is poor in detecting detailed structures like intimal flaps, thrombus, stent malposition, and tissue prolapse during stent implantation. ChromaFlo, a modality that shows blood flow by comparing sequential axial IVUS images and interpreting any differences in the position of echogenic blood particles as blood flow, has been used for optimal therapeutic strategies during PCI.[40]

OCT is a promising new technology that provides high-resolution (10-20 μm) intraluminal images with almost ultra-structural details. It consists of a fiberoptic wire that emits light in the near-infrared spectrum (1250-1350 nm) and records reflected light signals while rotating and being simultaneously pulled back along the long axis of a coronary vessel. OCT, however, has a poor penetration depth, but its high resolution allows visualization of microstructural features such as intimal tears, thrombus, or stent malposition. Unlike conventional time domain-OCT (TD-OCT) which requires coronary artery occlusion during imaging, newer generation frequency domain-OCT (FD-OCT) has faster image acquisition and greater scan depths without sacrificing the resolution of the image. OCT wire has a smaller diameter compared to the IVUS probe and has been described by Lim et al. as a useful adjunct in the management of patients with SCAD.[41] Recently, Zheng and colleagues have used dual-source computed tomography as a non-invasive method to diagnose SCAD.[42] Multi-detector CT (MDCT) can be also used to examine the extent and thickness of hematoma as well as to document healing and follow-up.[43]

There are no guidelines regarding optimal treatment of this condition. Treatment is guided by the clinical symptoms, extent and location of the dissection, and the hemodynamic status of the patient. Percutaneous coronary strategies are reasonable in acute cases with proximal dissection (of major epicardial vessels) and arterial occlusion in order to restore coronary perfusion and hemodynamic stability. Dissection of distal vessels of small caliber or with preserved blood flow (as in our case) without clinical or ECG changes may occur.

No data exists regarding use of drug-eluting stents (DES) over bare metal stents, although some have voiced concern that DES may adversely affect arterial healing. Cannulation of the false lumen and coronary perforation/occlusion are described as the potential complications of attempted intervention in SCAD. The major difficulty of stenting in the setting is that the intramural hematoma may be displaced either proximally or distally by the stent and results in luminal occlusion. One strategy is to deploy multiple stents, distal to proximal, covering the dissected portion of the artery; however, the risk is a greater chance of subsequent in-stent restenosis. The other strategy is to stent the entry point of the dissection if it can be visualized and to close the intimal defect with a stent and let the hematoma heal on its own. This, however, requires precise localization of the dissection entry point, which may be possible with OCT as described above.

Conservative medical therapy is reasonable in cases of distal dissection with preserved coronary flow. IVUS has been used to document healing of SCAD in select cases.[44] Reduction of vessel wall sheer stress with the use of beta-blockade has been described as a reasonable therapeutic choice.[45] The role of long-term antiplatelets in patients with SCAD, not receiving stent, has never been examined in a clinical trial; however, there are anecdotal evidences of benefit.[45] Use of heparin, thrombolysis, and glycoprotein IIb–IIIa inhibitors during the acute presentation is controversial.[46-49] The risks are extension of dissection or hematoma, and there is risk of postpartum hemorrhage or fetal intracranial bleeding during pregnancy and postpartum period.[50]

Surgical revascularization is usually restricted to hemodynamically unstable cases where percutaneous coronary intervention has failed (such as complete vessel occlusion due to expanding dissection) or is deemed impossible (such as multivessel long segment dissection with good distal segment suitable for bypass).[51]

A pubmed search yielded in excess of 500 articles, mostly case reports and case series. An inherent difficulty in understanding the natural history and prognosis of the condition is the rarity of its occurrence. Large-scale multicentric studies are necessary and novel strategies such as community-based social networking may be implemented to gather information about this disease.[52] The Discovery trial has been initiated as the first prospective registry to look into the incidence, therapeutic options, and outcome analysis for SCAD.[53]

Clinicians should keep in mind the possibility of SCAD in case of a pregnant woman with ACS. There is no apparent contraindication for using the usual medications like antiplatelets or beta-blockers, however ACE inhibitors should be avoided. Coronary angiogram, if necessary, should preferably be performed through a radial access along with a lead sheet over abdomen and pelvis of the patient, as it limits fetal exposure to radiation of less than 5 rad.

Internists as well as cardiologists should be familiar with the clinical presentation as well as angiographic appearance of SCAD and be aware of the treatment options. An understanding of the inherent difficulties and potential complications of manipulating dissecting coronary arteries should help guide the risk/benefit assessment of the therapeutic decision-making when confronted with this unusual angiographic finding.