Variations in Clinical Presentation, Risk Factors, Treatment, and Prognosis of Spontaneous Coronary Artery Dissection

Abstract: Spontaneous coronary artery dissection (SCAD) has been considered a rare cause of acute coronary syndrome (ACS) in younger patients without known cardiovascular risk factors. However, recent studies have reported a higher incidence of SCAD in patients presenting with ACS with use of advanced invasive imaging modalities. In light of increasing awareness, the diagnosis of SCAD has increased significantly. We conducted a single-center retrospective analysis of cases with reported SCAD during a 10-year period between 2003 and 2013. Ten cases of SCAD were identified after review of coronary angiograms and clinical records. Basic demographic details, comorbidities, initial presentation, length of dissection, specific vessels involved in dissection, initial management, subsequent outcome, and incidence of recurrence were documented. All patients were female, with mean age of 42 years. One-third of cases occurred in the peripartum period. All patients presented with acute coronary syndromes. The left anterior descending artery was the predominant vessel involved in 80% of the patients on initial presentation. Out of 10 patients, 6 were managed conservatively, 2 had emergent coronary artery bypass graft, and 2 had percutaneous coronary intervention with placement of stents. Three of the 6 patients undergoing medical management after the initial presentation had recurrence within the same hospitalization.  

J INVASIVE CARDIOL 2015;27(8):363-369

Key words: spontaneous coronary artery dissection, coronary stenting, intravascular ultrasound

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Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS). Its clinical presentation can vary from acute transmural ischemia with ST-elevation myocardial infarction (STEMI) and sudden death from ventricular arrhythmia to unstable angina. The description was made in 1931 in a young female patient who died suddenly.¹ Angiographic case reports followed later.² Initially, it was thought to be a very rare disease, with an incidence of about 0.1%-0.28%^3-5 in patients with ACS. However, more recent studies, which entail the frequent use of cardiac catheterization and advanced coronary imaging modalities such as optical coherence tomography (OCT) and intravascular ultrasound (IVUS), revealed that its incidence was likely underestimated.^6-8 A recently published study from Japan has estimated a prevalence of about 4% among all patients with ACS when OCT was used routinely on initial presentation with ACS.⁹

No guidelines exist for the management of patients with SCAD. Previous studies, including case reports, case series, and case registries, have identified several risk factors associated with SCAD. Young females in their early prepartum and postpartum periods have been identified as one of the important risk groups with increased prevalence of SCAD.^10,11 No association has been found with hypertension. However, increased sheer stress to the vessel walls during exercise and high output states like pregnancy could contribute to SCAD in these situations.^12,13 Also, SCAD has been described after cocaine intoxication.^14,15 Marfan’s syndrome and Ehlers-Danlos syndrome have been associated with SCAD in isolated cases.^16,17 Certain autoimmune conditions, vasculitis, cystic medical necrosis, and presence of eosinophilic infiltrates have also been described in patients with SCAD.^18-23 Weakening of the integrity of the vessel wall and/or vasa vasorum, whether due to an inflammatory condition or due to changes in connective tissue composition related to pregnancy, or possibly genetic molecular abnormalities, may contribute to the risk of SCAD in certain patient populations. 

Since the 2012 case series reported by Saw et al and the cohort study by Tweet et al in the same year, increasing awareness of SCAD was noted among interventional cardiologists.^6,7 We reviewed the incidence of SCAD diagnosis between 2012-2013 as compared with the years prior, and reviewed clinical risk factors, diagnostic features, treatment choices, and outcomes of documented cases of SCAD at our institution.

Methods

The study protocol was approved by the Indiana University institutional review board. We identified cases of SCAD by electronic search among adult patients >18 years of age who underwent coronary angiography between 2003-2013. Electronic medical records were reviewed. Coronary angiography was reviewed by two physicians. Patients with iatrogenic or percutaneous coronary intervention (PCI)-related dissections were excluded from the study. Patients with confirmed SCAD on coronary angiography were included for analysis. After this screening, 10 individual cases were identified who were diagnosed with SCAD based on angiographic and clinical findings. 

Definitions and variables. SCAD was identified on angiography based on typical angiographic appearance, including presence of an intimal flap, visualization of a false lumen, demonstration of SCAD on IVUS or OCT, or diffuse or defined segmental compression of coronary lumen by intramural hematoma with documented resolution on repeat angiography (type-2 or type-3 SCAD as per suggested classification according to Saw et al).²⁴ Demographics, comorbidities, clinical presentation, coronary distribution, length of dissection, initial and final treatment strategy (if different from the initial strategy), in-hospital outcomes, and subsequent follow-up (if available) were recorded. 

Results

We identified 10 patients with angiographically documented SCAD. The demographics are outlined in Table 1. The mean age was 42 ± 14 years. All 10 patients were female. Mean body mass index (BMI) was 28 ± 5 kg/m². Six out of 10 patients were Caucasian, and 4 were African-American. Three patients were in the peripartum period. A significant proportion were active (40%) or recent smokers (20%). Mean length of hospital stay was 6 ± 5 days. 

The clinical presentation of patients is described in Table 1. Four patients presented with acute ST-elevation myocardial infarction (STEMI), 3 presented with acute non-STEMI, 1 presented with sudden cardiac arrest, and 1 presented with ventricular tachycardia. The angiographic findings are summarized in Table 1. The left anterior descending (LAD) artery was the predominant vessel involved in 80% of the patients. One patient had isolated right coronary artery (RCA) involvement and 1 patient had multivessel SCAD with simultaneous involvement of both RCA as well as LAD. 

Table 2 demonstrates the initial management and clinical outcomes. The majority of patients (6/10) were managed conservatively, of which 50% (n = 3) had recurrence or progression of the dissection. Three patients underwent PCI as the initial management strategy; in 1 case, this led to retrograde expansion of a mid-LAD dissection into the left main and circumflex, requiring emergency coronary artery bypass graft (CABG). Two patients underwent CABG with successful outcomes and no recurrence. 

Likely as a result of increased awareness among interventional cardiologists, the incidence of SCAD on coronary angiography appears to have increased in recent years. Eight out of 10 patients in our study population were diagnosed between 2012-2013, whereas only 2 cases were reported as SCAD between 2003 and 2011. 

Case #1 was a young female patient who presented with anterior and inferior STEMI; coronary angiography demonstrated a dissection with significant intramural hematoma in the mid-LAD as well as a spiraling dissection in the RCA (Figure 1). Intracoronary nitroglycerin was administered with improvement in symptoms and coronary flow, as well as resolution of the ST elevation, and the decision was made to manage the patient conservatively. The patient was treated with vasodilators. After 2 days, chest pain recurred with worsening ST elevation in inferior leads. Repeat angiography showed near-complete resolution of the previous stenosis and dissection in the LAD; however, possible thrombus was noted in the distal RCA with continued TIMI-3 flow (Figure 1). Conservative management was continued, including anticoagulation and treatment with dual-antiplatelet therapy. Subsequent follow-up to 1 year was uneventful. 

Cases #2 and #3 had limited apical LAD involvement and were successfully managed conservatively. Case #4 presented with anterior STEMI and was found to have distal LAD dissection on initial angiography. Conservative management was pursued, given the resolution of chest pain and improvement in coronary flow. Two days after presentation, the patient had recurrence of chest pain and anterior ST elevation. Repeat coronary angiography demonstrated worsening of the dissection with involvement of the mid-LAD and first diagonal branch, with reduced TIMI-2 flow in the distal LAD (Figure 2). PCI was performed in the distal-mid LAD and resulted in retrograde expansion of the dissection to the ostial LAD, requiring placement of 4 long overlapping stents. Surveillance angiography and IVUS 1 month later revealed severe stent malapposition and severely undersized stents in the proximal to mid LAD (Figure 2). Further follow-up was uneventful, with plans for continued dual-antiplatelet therapy.

Case #5 presented with a focal intramural hematoma (type-3 SCAD) of a large obtuse second marginal branch, and was managed conservatively. Repeat coronary angiography 4 months later demonstrated complete healing of the culprit vessel.

Case #6 presented with cardiac arrest postpartum due to ventricular fibrillation with successful resuscitation by emergency medical providers. Coronary angiography demonstrated a hazy 40% stenosis in the mid-LAD with preserved TIMI-3 flow, and she was treated conservatively without clear identification of SCAD on angiography. She remained intubated, but after 2 days developed worsening heart failure symptoms, with rapidly progressive hypotension and tachycardia due to cardiogenic shock, and eventually pulseless electrical activity (PEA) arrest. Emergent repeat coronary angiography after resuscitation demonstrated retrograde expansion of the dissection into the proximal LAD, left main, and LCX artery, with TIMI-1 flow in the LAD and TIMI-0 flow in the LCX. Salvage PCI with stenting of the left main, LAD, and LCX was attempted; however, the patient expired due to refractory cardiogenic shock. 

Case #7 was postpartum and presented with inferior STEMI. Coronary angiography demonstrated compression of the ostial to mid RCA from intramural hematoma with TIMI-0 flow in the distal RCA (Figure 3). Manipulation of a Judkins right guide catheter resulted in opening of the dissection plane in the ostium of the RCA and restoration of TIMI-3 flow in the distal RCA (Figure 3). A guidewire was advanced into the distal RCA without difficulties and IVUS was performed in order to help identify the extent of the dissection. IVUS demonstrated that the location of the guidewire was within the false lumen, with complete compression of the native lumen and perfusion of the intact distal RCA through a reentry flap in the mid-RCA (Figure 3). Due to the extension of the dissection and inability to advance the guidewire through the true lumen, single-vessel CABG was performed successfully with favorable clinical outcome. 

Case #8 demonstrated initial dissection of the mid-LAD peripartum, which was successfully managed with PCI. Four years later, she presented again with another dissection in the RCA, which was also managed with PCI, but which was complicated by subacute stent thrombosis. 

Case #9 was a middle-aged female who presented with acute anterolateral STEMI due to SCAD and complete occlusion of the mid-LAD. An unsuccessful attempt was made to advance a guidewire across the mid-LAD occlusion, which led to extension of the dissection into the distal left main and LCX. Emergent CABG was performed successfully, with placement of 2 saphenous vein grafts to the LAD and LCX. 

Case #10 presented with acute non-STEMI, and coronary angiography demonstrated a tubular dissection in the mid-LAD. She underwent placement of a bare-metal stent, which required an additional overlapping stent to cover a distal extension of the intramural hematoma. 

Discussion

While previously thought to represent a rare condition, more recent studies have reported a SCAD incidence of up to 4% among patients presenting with ACS.⁹ The initial clinical presentation can vary from atypical angina to acute STEMI with cardiogenic shock and sudden cardiac death.^3,4,13 Classic angiographic features of SCAD with clearly defined intimal tear or spiraling dissection may not be evident, especially if the coronary dissection is contained and limited to intramural hematoma. When SCAD is suspected, invasive imaging modalities such as IVUS and OCT is advocated, if they can be performed safely. There should be a high suspicion for SCAD in young patients without classic cardiovascular risk factors who present with ACS; however, SCAD may also present in middle-aged patients with cardiovascular risk factors. 

No guidelines exist for the management of SCAD. It has been suggested that patients without ongoing ischemia, preserved coronary flow (TIMI-3), single vessel involvement, or distal vessel involvement may benefit from conservative medical management. However, these patients are at risk of progression of the dissection, retrograde extension, simultaneous involvement of other major epicardial vessels, and recurrent acute myocardial infarction. Age, anatomic features, extent of SCAD, and clinical presentation contribute to large variability in clinical outcomes, and mandate individualization of clinical decisions regarding optimal management in each patient. PCI in the setting of SCAD is associated with particular challenges. Identification of the true lumen during guidewire insertion may be difficult and can lead to extension and worsening of the dissection. Similarly, repeated injections of contrast dye through guide catheters can further propagate SCAD located in proximal sections of coronary arteries. Stent deployment in SCAD cases commonly leads to compression and propagation of the intramural hematoma, which can be associated with unpredictable antegrade and retrograde extensions of the coronary dissection. This often leads to placement of multiple overlapping long stents to preserve patency of the coronary lumen. Therefore, in patients who have preserved coronary flow beyond the site of dissection and extensive hematoma within the vessel wall, stenting should likely be avoided. It has been suggested to stent only the proximal portion of the dissection, or to target the presumed entry point of the hematoma as identified by OCT or IVUS, with the aim of sealing the flap/entry point and allowing the hematoma to heal. Late stent malapposition after healing of the SCAD is likely a common feature associated with PCI in the setting of SCAD and significantly increases the risk of late stent thrombosis. 

CABG has been performed successfully in patients with SCAD, but carries its own specific technical challenges. Often, the lack of structural integrity of target vessels increases the difficulty in obtaining optimal anastomotic results. Similarly, decreased coronary run-off increases the risk of graft occlusion. CABG may be a suitable revascularization strategy when a flow-limiting dissection is localized in the proximal segment of a major epicardial vessel with intact distal target vessels for bypass.²⁵ 

The results of our study are consistent with findings from larger case series. Demographics and clinical features of our patient population were similar to those in larger studies by Saw et al and Tweet et al. The observed mean age of 42 years in our case series was close to the mean age reported in those larger study populations. All patients in our case series were female, compared with ~80% female gender prevalence in other studies. The most common condition associated with SCAD is peripartum state, which was reflected in our study as well. STEMI was the predominant clinical presentation, with the LAD being the most common culprit vessel, which is consistent with findings from previous studies. 

Previous studies have indicated that patients managed conservatively may exhibit spontaneous healing of the dissection and favorable clinical outcomes. Of note in our study, one-half of the patients who were managed conservatively had recurrence of symptoms and worsening of the dissection within the same hospitalization. One of the 6 patients who was treated conservatively demonstrated extension of the LAD artery SCAD, resulting in retrograde involvement of left main and compromise of the LCX, resulting in fatal cardiogenic shock a few days after initial presentation. Another patient with multivessel SCAD, including an extensive dissection of the LAD, was managed medically and demonstrated resolution of the initial LAD dissection on repeat angiogram 2 days later. A third patient with recurrence of ischemia after 2 days underwent PCI with multiple overlapping stents in the LAD, which were found to be significantly malapposed and undersized on repeat angiography. The remaining 3 patients had only distal vessel involvement and the length of the dissection was also relatively short, which may be a predictor of favorable outcomes with conservative management.

Beta-blockers have been shown to be beneficial in reducing sheer stress in patients with aortic dissection and thus might be useful in the treatment of patients with SCAD. There is inconclusive evidence regarding the potential risk-benefit of anticoagulation with heparin or use of glycoprotein IIb/IIIa inhibitors. Anticoagulation may prevent the thrombosis related to exposure of subendothelial matrix and acute vessel closure, but also prevent thrombosis of the false lumen and theoretically promote bleeding from vasa vasorum with possible expansion of intramural hematoma.^26-34 The role of antiplatelet therapy in the short term and long term in patients not being treated with PCI is also controversial.³⁵

We did not observe a correlation between SCAD and fibromuscular dysplasia, as described in recent studies. However, none of our patients underwent specific imaging tests to screen for fibromuscular dysplasia. 

In our case series, survivors of the initial event demonstrated a favorable outcome. Previous studies have reported similar findings. In-hospital mortality has been reported to be 3% in larger series,^36,37 but this may possibly be an underestimation. Patients who survive the acute phase have a low recurrence of SCAD³⁸ and good prognosis, with a reported 2-year survival rate of around 95%.³⁹ While SCAD is relatively common among young women in the peripartum period, it may also occur in middle-aged patients presenting with ACS. Early identification and appropriate rapid intervention with advanced hemodynamic support, such as left ventricular assist devices or extracorporeal membrane oxygenation, is advised in patients presenting with cardiogenic shock secondary to extensive SCAD. 

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From the Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kreutz reports consulting fees from Coramed. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted August 25, 2014 and accepted October 10, 2014.

Address for correspondence: Rolf P. Kreutz, MD, FACC, FAHA, FSCAI, Assistant Professor of Clinical Medicine, Krannert Institute of Cardiology, Indiana University School of Medicine, 1800 N. Capitol Ave, ME-400, Indianapolis, IN 46202. Email: rkreutz@iu.edu