Spontaneous Coronary Artery Dissection: Case Series and Review
ABSTRACT: Spontaneous coronary artery dissection (SCAD) is a rare but important cause of acute coronary syndromes. SCAD can cause unstable angina, acute myocardial infarction, and sudden death. Predisposing factors include atherosclerosis, the peripartum period, and structural and inflammatory conditions affecting the arterial wall. The diagnosis of coronary dissection is usually made by coronary angiography. Prompt diagnosis and treatment of patients with dissection improves survival. Therapeutic options include medical therapy, percutaneous coronary intervention, and surgery. We present a series of patients with spontaneous coronary artery dissection at our institution. The etiology, pathogenesis, diagnosis, treatment, and prognosis of patients with coronary dissection are reviewed.
J INVASIVE CARDIOL 2008;20:553–559
Spontaneous coronary artery dissection (SCAD) is a rare condition that can result in unstable angina, acute myocardial infarction, and sudden death. The diagnosis of coronary artery dissection is usually made by coronary angiography. There is increased recognition of SCAD due to frequent utilization of coronary angiography, especially in acute coronary syndromes. Management of SCAD can be challenging: clinical presentation ranges from asymptomatic to unstable angina, acute myocardial infarction, ventricular arrhythmias, and sudden death. Various treatment options have been utilized, including medical therapy, percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery. The current understanding of the etiology, pathogenesis, diagnostic imaging, and approaches to management of SCAD are reviewed.
Definition. Coronary artery dissection can occur spontaneously or as a consequence of chest trauma, cardiac surgery, coronary angiography, coronary intervention, or as extension of aortic dissection. Coronary arteries are comprised of three layers: the intima, the media, and the adventitia. Dissection of the coronary artery results in separation of the layers of the arterial wall, creating a false lumen. The separation may be between the intima and the media, or between the media and the adventitia. Hemorrhage into the false lumen can impinge upon the true lumen of the coronary artery, impairing blood flow and causing myocardial ischemia, infarction, or sudden death.1–3
Incidence. The first case of spontaneous coronary dissection (SCAD) was described in 1931.4 About 300 documented cases of SCAD have been reported; this is likely an underestimate due to a significant number of spontaneous dissections presenting as sudden death.5,6 Many cases have been diagnosed only at autopsy. The overall incidence of SCAD in angiographic series ranges from 0.28 % to 1.1 %.7,8 There is a predominance of SCAD in young women.9 Seventy percent of SCAD occurs in women; of that, approximately 30% occurs in the peripartum period.9,10 The left anterior descending artery is the most frequent location of dissection. In angiographic and autopsy series, the LAD accounts for over 60% of coronary dissections.9,10
Pathogenesis. The most common conditions associated with SCAD are coronary atherosclerosis8,9 and the peripartum period.11,12 There are different possible mechanisms of coronary dissection. Atherosclerotic plaque inflammation and rupture may cause disruption of the intimal-medial junction, resulting in an intimal flap and subsequent intramural hematoma formation. In contrast, peripartum dissection is not associated with the presence of coronary artery atherosclerosis but has been associated with the presence of eosinophils. Eosinophilic infiltrates have been described in the coronary artery adventia in autopsy studies of SCAD without coronary atherosclerosis.13 Eosinophil granules contain numerous lytic substances, including collagenase, peroxidase, major basic protein, and acid phosphatase.14 These substances may break down the medial-adventitial layers and lead to dissection (in contrast to intimal-medial dissection associated with atherosclerotic disease). During labor and the peripartum period, eosinophils infiltrate the uterus and serum collagenase levels increase. The presence of eosinophils in dissected coronary arteries may be a systemic manifestation of this process.14 In animal studies, estrogen and progesterone can induce eosinophils to release granules that contain lytic substances.15,16 Elevations of estrogen and progesterone occur during pregnancy and the peripartum period. In addition, during pregnancy there are microstructural changes in the elastic and collagen fibers of the tunica media of the aorta that may be caused by hormonal and hemodynamic factors.17 These changes could also occur in the coronary arteries, possibly contributing to the predisposition to dissection in the peripartum period.9
Spasm may increase the shear stress on coronary arteries and lead to dissection. Variant angina has been associated with spontaneous coronary dissection.7,18 Cocaine causes coronary spasm and vasoconstriction,19 and coronary dissection has been reported with cocaine use.20 Eosinophils may play a role in spasm as well. In an animal model, extracts from eosinophils caused strong contraction of intestinal smooth muscle.21 It is possible that eosinophilic products can trigger coronary spasm in humans.
Various other conditions have been associated with SCAD. Hypertension may be a risk factor for coronary dissection.22 Cystic medial necrosis can occur with hypertension: it is characterized by fragmentation of elastic fibers and loss of smooth muscle cells in the tunica media, which can weaken the arterial wall and predispose to dissection.23 Conditions that cause abnormalities in arterial wall structure, including Marfan’s syndrome,24 Ehlers-Danlos syndrome,25 and lysyl oxidase deficiency have been associated with SCAD.26 Vasculitis, including polyarteritis nodosa,27 systemic lupus erythematosus,28 and isolated eosinophilic arteritis29 can involve the coronary arteries: it is possible that localized inflammation can break down the components of the arterial wall. There have been reports of spontaneous dissection in patients with antiphospholipid syndrome30 and inflammatory bowel disease.31 Medications such as oral contraceptives,32,33 cyclosporine,34 5-fluorouracil,35 and fenfluramine36 have been associated with SCAD. Excessive exercise has been linked to dissection; exercise results in a hyperdynamic state and may increase mechanical stress on the coronary arteries.37 However, SCAD may also occur in patients without any risk factors.38
Imaging. The typical appearance of coronary artery dissection on coronary angiography is a thin radiolucent line representing the intimal medial flap, with flow in two separate lumens (Figure 1). The caliber of the artery may be irregular, and haziness may be present indicating thrombus formation, especially during acute coronary syndromes (Figures 2 and 3). Rarely, the artery appears narrowed without evidence of intimal flap (Figure 4). This can occur when there is no flow of contrast through the false lumen, for example in dissections with an entry point but no exit, or in dissections limited to the medial-adventitial layers. In these cases, intravascular ultrasound (IVUS) can visualize the dissection flap. The false lumen is often filled with organizing thrombus, which appears heterogeneous and speckled (Figure 5). The false lumen lacks the three layer appearance (intima, media, and adventitia) of the normal arterial wall. Occasionally a dissection entry point can be visualized (Figure 6). Chronic, healed dissections do not impair coronary flow and typically do not appear hazy on angiography.
Diagnosis and Management. Patients with spontaneous coronary dissection may present with unstable angina, non ST elevation myocardial infarction, ST-elevation myocardial infarction, or congestive heart failure. Occasionally, spontaneous dissection is diagnosed during cardiac catheterization for chronic stable angina or valvular heart disease. The diagnosis of SCAD is usually made by coronary angiography. There is increased recognition of SCAD due to advances in imaging modalities, including coronary angiography, intravascular ultrasound, and CT angiography. Patients with unstable angina and acute myocardial infarction frequently undergo early cardiac catheterization, which leads to definitive diagnosis and treatment. Spontaneous coronary artery dissection should be suspected in young women with acute coronary syndromes, especially in the peripartum period.
When cardiac catheterization is not available, SCAD patients presenting with acute ST elevation myocardial infarction have been treated with thrombolytics. However, there have been reports of clinical deterioration after thrombolysis, and subsequent cardiac catheterization showed extensive coronary dissection.39,40 Coronary obstruction in SCAD is not due to intraluminal thrombus; instead, an intimal flap with intramural hematoma compresses the lumen, and thrombolytics may promote extension of the dissection. This illustrates the importance of definitive diagnosis with angiography.
Treatment options for SCAD include medical therapy, percutaneous coronary intervention (PCI), or coronary artery bypass graft surgery. The decision to treat medically or perform percutaneous intervention or surgery must be individualized based on both clinical and angiographic factors (Figure 9). Dissection of large coronary arteries causing persistent ischemia is usually treated with percutaneous intervention or surgery, while dissections of small vessels are treated medically.
When there is no evidence of persistent ischemia or hemodynamic instability, medical therapy alone may be utilized.41,42 Treatment of spontaneous coronary dissection is similar to treatment of acute coronary syndromes. This includes anticoagulation with heparin or enoxaparin,41 aspirin, clopidogrel,43 beta-blockers, and nitrates. Calcium channel blockers may be used to treat spasm.
Medical therapy has been used successfully to stabilize and treat coronary dissection.42 Glycoprotein IIb/IIIa inhibitors have been utilized to treat ischemia due to coronary dissection44 and are often given prior to coronary angiography for high risk unstable angina and non ST-elevation myocardial infarction, before the diagnosis of coronary dissection is known. Glycoprotein IIb/IIIa inhibitors may be used as adjunctive therapy during percutaneous intervention for unstable dissections; however, there is a theoretical risk of hematoma expansion with these agents and more data are needed.
Dissection of epicardial vessels causing flow impairment or persistent ischemia should be considered for treatment with percutaneous intervention or surgery.8 Percutaneous intervention with stenting can restore flow in the true lumen, relieving ischemia, and seal the dissection, preventing further expansion. Intravascular ultrasound can aid in diagnosis, particularly when an angiographic intimal flap is not evident. Technical issues during percutaneous coronary intervention include placing the guidewire in the true lumen rather than the dissection plane and ensuring sealing of the dissection entry point with an appropriately sized stent. IVUS can be used to confirm guidewire placement in the true lumen, evaluate the length of dissection and vessel size, and assess stent apposition and sealing of the dissection (Figure 7). The clinical success rate of stenting in patients with SCAD is over 90%.45 Single vessel dissections are usually treated with percutaneous intervention with stenting, while left main dissection, multivessel involvement, or failure of percutaneous interventional procedures may require surgical intervention.1
Coronary artery bypass graft surgery can be challenging in cases of spontaneous dissection. In particular, grafting to the true lumen may be difficult, especially with long dissections involving the entire vessel.5 The vessel wall may be fragile due to the underlying condition predisposing to dissection. Surgical treatment can address other pathological conditions, including significant valvular heart disease or aortic aneurysm.
Outcomes after percutaneous intervention and surgery are favorable. In the largest reported single center series of 42 consecutive patients with SCAD, 24 were treated with stenting, 7 with balloon angioplasty, 8 with coronary artery bypass surgery, and 3 with conservative medical therapy. At a mean follow up of 13.5 months, 31 of the 42 patients were asymptomatic; there were 2 recurrent dissections and 2 mortalities.8 These data are consistent with acceptably low rates of recurrent ischemia, dissection, and mortality after invasive therapy. Limited data are available on drug eluting stents in SCAD. It is reasonable to extrapolate that drug eluting stents decrease restenosis rates, especially if the dissection is long; however, more data are needed.
Our Experience. In our center, there have been four cases of angiographically documented spontaneous coronary dissection. This series illustrates the varying presentations and management of spontaneous coronary artery dissection. The indications for angiography included acute ST elevation MI, non ST elevation MI, and unstable angina (Table 1).
The first patient had end stage renal disease and hypertension, and presented with unstable angina and pulmonary edema. Cardiac catheterization showed a tortuous, calcified right coronary artery with dissection in the mid segment (Figure 1). Medical therapy was chosen over PCI due to complicated lesion morphology. Cardiac enzymes remained negative, and the patient was treated medically.
The second patient had an angiographically documented history of diffuse coronary spasm, rheumatic heart disease, and mitral valve replacement, and presented with non-ST segment elevation myocardial infarction. Cardiac catheterization showed dissections in multiple vessels (Figures 2 and 3). Of note, the dissections developed while on warfarin anticoagulation for the mechanical prosthetic mitral valve. Due to the location of the dissections in small distal vessels, the patient was treated medically.
The third patient presented with ST-segment elevation myocardial infarction. There was diffuse narrowing of a long segment of the LAD without angiographic evidence of dissection (Figure 4). Intravascular ultrasound was performed, which demonstrated a dissection starting at the ostium of the LAD and extending to the mid LAD, and a thrombus-filled false lumen compressed the true lumen (Figures 5 and 6). This case demonstrates the clinical utility of intravascular ultrasound in the diagnosis of spontaneous dissection. The patient was treated with a drug-eluting stent (Figure 7). Subsequent myocardial perfusion imaging revealed no evidence of ischemia.
The fourth patient presented with unstable angina and left heart failure. Cardiac catheterization showed spontaneous dissection of the proximal RCA (Figure 8). Left ventriculography revealed severe left ventricular systolic dysfunction and severe mitral regurgitation. The patient was treated surgically with mitral valve repair and coronary artery bypass grafting.
Despite the common angiographic finding of spontaneous coronary dissection, the clinical presentation and management of each patient was different. Successful treatment strategies included medical therapy, percutaneous intervention, and surgery. At one year follow up, all patients remain asymptomatic and free of ischemia.
Recommendations. There are no randomized trials of coronary dissection treatment; the literature consists of case reports and case series. The clinical presentation should guide initial therapy. The diagnosis of SCAD should be considered in the differential diagnosis of chest pain, especially in younger patients, peripartum women, and patients with underlying connective tissue disease.
Patients presenting with ST elevation myocardial infarction are increasingly treated with primary PCI. If SCAD is suspected, thrombolytics for ST elevation myocardial infarction should be avoided, and patients should be referred for primary PCI, where the diagnosis of coronary dissection can be made by coronary angiography. Patients with unstable angina or non-ST elevation myocardial infarction should be considered for early cardiac catheterization. Glycoprotein IIb/IIIa inhibitors may be started upstream for high risk features of acute coronary syndrome such as positive cardiac enzymes. If SCAD is diagnosed on angiography, percutaneous intervention or surgical treatment can be performed as appropriate.
Medical therapy for all patients should include anticoagulation with heparin or low molecular weight heparin for 48–72 hours, aspirin, clopidogrel, beta-blockers, and nitrates. Antiplatelet therapy should continue for at least 6–12 months, especially if a stent has been placed. The underlying etiology of SCAD should be ascertained. For patients with coronary artery disease, medical therapy with aspirin, beta-blockers, and cholesterol lowering medication should continue indefinitely. Patients with coronary spasm should be treated with calcium channel blockers and nitrates. Patients who experienced peripartum dissection should be counseled against future pregnancies, as the risk of dissection increases with multiparity and increasing age.12
Patients should be followed clinically for symptoms of recurrent ischemia. Routine angiographic follow up is not recommended. Stress testing with nuclear perfusion imaging is reasonable for surveillance, especially in patients with dissections of large vessels with large areas of myocardium at risk.
Prognosis. The prognosis of patients with SCAD has improved in recent years, likely due to increased diagnosis by cardiac catheterization and advances in treatment. In earlier series, mortality from spontaneous dissection was approximately 50%.1 If the patient survived the original episode, subsequent survival was 80%, and approximately 50% of patients experienced a recurrent dissection within two months.1 With contemporary medical therapy, the rate of recurrent dissection is much lower and most patients are asymptomatic at follow up, with a 95% survival and 5% recurrent dissection rate.8 A recent analysis of all published cases of SCAD showed that after 1990, survival of patients with spontaneous coronary dissection approached 90%.10 Predictors of mortality on multivariate analysis included female sex and failure to recognize and treat the dissection. All types of treatment modalities (medical therapy, percutaneous intervention, or surgery) improved survival. There was no difference in survival among the different treatment modalities.10 These data suggest that prompt recognition and targeted treatment of this disorder improves outcomes.
Conclusions. SCAD is an uncommon but important cause of unstable angina, myocardial infarction and sudden death. Predisposing conditions include atherosclerosis and the peripartum period. Weakening of the arterial wall and eosinophils may play a role in the development of spontaneous dissection. Diagnosis of the condition with prompt coronary angiography is important for proper management. Treatment options include medical therapy, percutaneous intervention, and coronary artery bypass surgery. SCAD has a favorable prognosis with current medical and interventional therapy.
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