Spontaneous coronary artery dissection (SCAD) is a very rare cause of acute coronary syndromes in young, otherwise healthy patients, with a striking predilection for the female gender. It was reported for the first time in 1931 at the autopsy of a 42-year-old woman.1 Since this first report, there have been about 160 case reports, the majority of which were diagnosed postmortem. The clinical presentation of SCAD depends on the extent and severity of the dissection, and ranges from unstable angina to sudden cardiac death. Although the pathological mechanism is not fully understood, several diseases and conditions have been associated with SCAD.
This implies that SCAD is possibly a heterogeneous disorder in which more than one therapeutic regimen should be considered. In this report, we present the case of a young woman who presented with an acute coronary syndrome and sudden cardiac death due to SCAD, and will present a review of the literature and elaborate on the pathogenesis, therapeutic options, and prognosis.
A 29-year-old female who delivered a male baby seven days back as normal delivery in hospital presented to the hospital emergency service/room (ER) with history of generalized vague abdominal pain with nausea. Her vitals in the ER included pulse 145/min, blood pressure 100/60 mmHg, respiration at 20/min. Basic lab work for CBC, Chem-7 was sent. The emergency physician admitted her under gastrointestinal (GI) service and the patient was admitted to a private suite with symptomatic intravenous (IV) medications. The patient suddenly collapsed as she reached the suite and became unconscious. We, from the cardiology service, were called at this time. The patient had ventricular fibrillation on the cardiac monitor. She was successfully revived with a 200-Joule DC shock, and was intubated and put on a respirator. She was pulseless and had no recordable blood pressure; appropriate pressor agents were immediately started. She had already had an electrocardiogram (ECG) done by her primary care physician. These ECGs were shown to us later on (Figures 1-3). We made a diagnosis of anterior wall myocardial infarction (AMI), and with the possibility of spontaneous coronary artery dissection, suggested to the family that coronary angiography be done, though the patient was pulseless, with a heart rate of 145 beats/min, and no recordable blood pressure at this stage. The family signed a high-risk consent with the possibility of death on the cath table. On coronary angiogram, the patient was found to have a coronary artery dissection with thrombotic occlusion of the left anterior descending artery (LAD). The family consented and signed for a high-risk percutaneous coronary angioplasty (PTCA). The patient was loaded with clopidogrel and after crossing the lesion with a guide wire, a drug-eluting coronary stent was placed (Figures 4-6). Coronary flow was immediately restored, her blood pressure recovered to 90/60 mmHg, and after a few hours, she was successfully extubated, regaining consciousness with no residual neurological deficit. Since the patient was on clopidogrel, she was advised to feed her baby with formula only (also, for unknown reasons, lactation could not be established). She had a left ventricular ejection fraction (LVEF) of about 20% pre-procedure and has now recovered to 35% after six months. The patient has been advised to refrain from further pregnancies because of her pregnancy-related coronary artery dissection.
SCAD is a very rare condition with an incidence of 0.1% for patients referred for coronary angiography.2 Since SCAD may often lead to death in the preclinical phase and dissections of the coronary arteries are difficult to recognize, many authors believe the incidence is underestimated.3 The mean age at presentation is 35 to 40 years, and more than 70% of SCAD cases are women.4 Classically, the patients are divided into four groups: (a) peripartum, (b) atherosclerotic, (c) idiopathic, and (d) with connective tissue disease with vasculitis.4 However, this classification does not cover all possible underlying conditions causing SCAD.
More than a third of all SCAD cases occur in the peripartum period, of which one-third are in late pregnancy and two-thirds in the early puerperal period.4,5 The peak incidence is in the second week after delivery.6 The earliest reported case occurred within nine weeks of conception and the latest, three months postpartum. In one review, only 30% of reported peripartum SCAD patients had known risk factors for coronary artery disease.6 The role of the peripartum period in the pathogenesis is still unclear. Changes in the levels of sex hormones are considered to play an important role. High levels of estrogens are thought to change the normal arterial wall architecture, resulting in susceptibility to spontaneous dissections. These changes include hypertrophy of the smooth muscle cells, loosening of the intercellular matrix due to an increase in acid mucopolysaccharides, and decreased collagen production in the media.7-9 On top of these changes, elevated cardiac output, increased total blood volume, and straining and shearing forces during labor may result in increased wall stress. Thus, both hormonal and hemodynamic changes in pregnancy are thought to increase the risk of intimal tears in the arterial wall and coronary artery dissections.
There are several conditions other than pregnancy that have been associated with SCAD. In about 30% of SCAD patients, an underlying cause other than pregnancy can be identified, most frequently, atherosclerotic plaque(s) rupture.4 Several lines of evidence suggest that mild atherosclerosis is even more often the underlying cause than assumed previously.10-11 Celik et al even reported that all their non-pregnant patients had a certain degree of atherosclerosis.12 With the help of intravascular ultrasound (IVUS) studies, Hering et al demonstrated that in 35 of 42 SCAD patients, underlying atherosclerotic disease was detectable.13 The pathophysiological mechanism appears to differ from the spontaneous dissection in pregnancy. An increased density of vasovasorum due to atherosclerotic plaque formation may cause bleeding and even rupture, which can lead to dissection of adventitia from media and may result in a rupture of the intima.14
In significant number of cases, an underlying condition that may lead to SCAD cannot be identified at all and it is subsequently classified as idiopathic. Although there is a weak association with smoking and hypertension15, the affected individuals do not usually have conventional risk factors for atherosclerosis at all, are young and healthy otherwise, and are mostly female.
Connective tissue disease with/without vasculitis
In the minority of cases, SCAD can be associated with connective tissue diseases such as Marfan’s syndrome and Ehlers-Danlos type IV. In these connective tissue disorders, a medial degeneration of the coronary arteries is thought to lead to weakness of the arterial wall and increased susceptibility to spontaneous dissections.16-17 An association between SCAD and systemic lupus erythematosus (SLE) has also been reported.18-19 In SLE, a general vasculitis is considered to be the pathological mechanism leading to chronic inflammation of the vessels and susceptibility to spontaneous dissections. In several other case reports, an association is described between SCAD and a certain condition such as vigorous exercise20, prolonged sneezing21, or cocaine abuse, in which coronary spasms are thought to cause dissections.22 Some authors also posed a relationship between the use of oral contraceptives and the menstrual cycle.23
SCAD is thought to be the consequence of an intramural hematoma of a coronary artery, resulting in a false lumen that compresses the true lumen, with subsequent myocardial ischemia.3 The clinical presentation of SCAD depends on the extent and severity of the dissection, and ranges from unstable angina to sudden cardiac death. The pathological mechanism leading to this dissection depends on other underlying disease, if present. Patients with SCAD can present with a broad spectrum of symptoms, from an acute coronary syndrome to out-of-hospital cardiac arrest, heart failure, or even sudden cardiac death. When a young woman without any risk factors presents to the hospital with one of these previously mentioned clinical features, the clinician should have a high grade of suspicion for SCAD and emergency angiography should be considered. Dissection of the left anterior descending artery is the most common location in women, whereas right coronary artery dissection is most common in men.3–4 Recognition of the dissection can be quite difficult and may require multiple angiographic views or IVUS to confirm the diagnosis.10,11,24
Treatment and diagnostic workup
There is no specific guideline to treat a spontaneous coronary artery dissection. In case of presentation with an acute myocardial infarction with ongoing ischemia, the first objective should be to restore normal coronary flow. Fibrin-specific thrombolytic drug therapy is discouraged, because it may result in further propagation of the dissection due to progression of the intramural hematoma.25 Primary percutaneous coronary intervention (PCI) remains the reperfusion strategy of choice. If the vessel is open and the flow normalized at the time of angiography, it is defendable to treat the dissection conservatively. Good angiographic and clinical outcomes have been described with medical treatment only also.2,26 With conservative measures, coronary artery dissections have even shown complete angiographic resolution after a year2,20,21, and this approach still seems wise in small and medium-sized vessels with normal flow. However, when it is a large epicardial vessel, placement of a stent will often be the treatment of choice. In case of multivessel or left main involvement, several case reports also describe treatment with urgent surgical revascularization.24 Our patient had features of anterior wall myocardial infarction and angiography revealed spiral dissection of the LAD. With the agreement of the family, we opted for urgent percutaneous coronary angioplasty (PTCA) with stent implantation and were able to successfully revive the patient.
The phase after the event should not only be used for the patient to recover from the infarction, but also to evaluate the possible cause of SCAD, because it affects the choice of therapy. Treatment should be tailored to the individual. Coronary angiography as well as IVUS will help to identify signs of coronary atherosclerosis. In case of atherosclerosis, aggressive measures should be taken to stabilize atherosclerotic plaques. These measures include aggressive lipid lowering by statins, β-blockade, antihypertensive therapy, and antiplatelet therapy. However, when there are no signs of atherosclerosis in the coronary arteries, statins are not indicated, although β-blockers and platelet inhibitors do need to be continued after discharge. Whether to use aspirin or clopidogrel or both in conservatively treated patients remains debatable.2 In lactating mothers, clopidogrel is contraindicated.
Pregnancy testing should always be performed in premenopausal women. If an SCAD patient is indeed pregnant, statins and ACE inhibitors should not be given, due to their teratogenic effects. A connective tissue disease should be suspected from a positive family history or abnormalities on physical examination. There is assumed to be an association between SCAD and two connective tissue disorders, namely Marfan’s syndrome and Ehlers-Danlos type IV. Marfan’s syndrome is an autosomal dominant inheritable disorder caused by a mutation in the FBN1 gene. However, 25% of Marfan’s syndrome cases do not inherit the FBN1 gene, but are due to new mutations. Although it has a variable phenotypic expression, Marfan’s syndrome may present with symptoms of the skeletal, cardiovascular and ocular system. Skeletal manifestations are a reduced upper to lower body segment ratio, arm span exceeding height, and arachno-dactyly with hyper laxity of the joints. Cardiovascular symptoms are aortic insufficiency, aortic aneurysms, mitral valve prolapse, and insufficiency. Manifestations of the ocular system are ectopia lentis. If the diagnosis is suspected, genetic testing for a mutation in the FBN1 gene can be performed.27
The other connective tissue disorder is Ehlers-Danlos syndrome. This syndrome combines a group of six forms of disorders that share hyperelasticity, fragility of the skin, and hyper mobility of the joints. Ehlers-Danlos type IV is also called the vascular type, and is an autosomal dominant disorder characterized by spontaneous rupture of large and medium-sized arteries. In contrast to the other groups of Ehlers-Danlos, joints in the type IV group are only mildly hyper mobile. However, there are some very characteristic facial features, including a thin, delicate, pinched nose, thin lips, hollow cheeks and prominent, staring eyes, because of absence of adipose tissue in this region. In addition, there is thin, translucent, and easily bruising skin that is usually mildly elastic. If the diagnosis of Ehlers-Danlos syndrome type IV is suspected, it can be confirmed by performing genetic testing and skin biopsies to analyze collagen obtained from cultured fibroblasts.28
SLE may also lead to spontaneous dissections due to two possible mechanisms: associated atherosclerosis and vasculitis. SLE is a chronic inflammatory disease of unknown cause that can affect almost every organ. It should be suspected when there are non-specific symptoms such as fever, fatigue, weight loss, or anemia. A complete blood count and differential, inflammatory parameters (C-reactive protein level, erythrocyte sedimentation rate), and antinuclear antibodies (ANA) should be measured. If these parameters are normal, a vasculitis caused by a chronic inflammatory disease such as systemic lupus erythematosus is unlikely.29 Thus, referral and further work-up, such as imaging, skin biopsies, and genetic testing, is only indicated when there are typical findings for a connective tissue or systemic disorder.
Our patient was in the postpartum state and hence, her SCAD was related to only to pregnancy. Since she was being managed by a team of gynecologists, initial suspicions focused on a postpartum-related state with possible retained product of conception/placenta or gastrointestinal illness. Despite three ECGs done at an outside facility, diagnosis of myocardial infarction was not even considered. When our cardiology team was summoned for help on her sudden collapse, a diagnosis of AMI with possibility of SCAD was considered and appropriately managed with coronary angiography followed by coronary angioplasty with stent implantation. Whether the patient’s left ventricular dysfunction is secondary to her coronary lesion or part of peripartum cardiomyopathy is anybody`s guess, as no echocardiography was done prior to delivery of the baby.
The overall peri and post procedure mortality in reported cases of the peripartum group is 38%.6 Patients with underlying atherosclerosis are thought to have a better prognosis due to the presence of collateral circulation which may develop due to chronic atherosclerosis.13 Men tend to have a better chance of survival compared with women, who have an even worse prognosis when they are not in the peri- or postpartum period.3,4 In general, it can be stated that the long-term prognosis of patients with SCAD is favorable, if they survive the acute phase.2 In a review comprising 152 cases over the last 50 years, Kamineni et al reported that 50% of patients with SCAD developed a recurrent dissection within two months. This suggests an enhanced susceptibility to spontaneous dissections in the acute phase. The high chance of developing a recurrent dissection is indicative of a general vessel weakness. This hypothesis is confirmed by the observation that in more than 40% of pregnant SCAD patients, dissections could be demonstrated in more than one vessel.6 It seems that for these patients, there is a systemic susceptibility to dissections at a certain point in life, marked by the initial event during pregnancy.
SCAD is a rare, often pregnancy-related state, and a multifactorial and complex disease that occurs predominantly in young, otherwise healthy subjects. Strong clinical suspicion is key to diagnosis. Its presentation varies from unstable angina to sudden cardiac death. In the acute phase, primary PCI remains the reperfusion strategy of choice; however, in small and medium-sized arteries with normalized TIMI flow, conservative treatment is defendable. Further medical therapy should be tailored to the individual, depending on the underlying condition. Patients have a high risk of recurrent dissections in other arteries several weeks after the first event, suggesting a generalized weakness of the arterial walls. The prognosis appears to be good, if the patient survives the acute phase.
“Spontaneous Coronary Artery Dissection in the Post-Partum Period: A Pregnancy-Related Phenomenon”
Sameer Mehta, MD, Olga Reynbakh, MD, Jennifer Kostala, MD, Daniel Rodriguez, MD, Lumen Foundation, Miami, Florida
Medical literature is brimming with exotic illnesses that have fatal outcomes, but that do not come to the forefront of differential diagnosis on account of the rarity of their presentation.
The biggest take-home lesson from “Spontaneous Coronary Artery Dissection in the Post-Partum Period: A Pregnancy-Related Phenomenon” by Dr. S.K. Chutani is the critical importance of physician and institution awareness of rare but deathly clinical entities.
The case study of the 29-year-old pregnant patient is a well-written document of a well-managed patient. The diagnosis of acute myocardial infarction (AMI) from a very atypical presentation was brilliant and follow-up management was exemplary. Angiography and percutaneous coronary intervention (PCI) were expediently performed with considerable skills. Post-PCI management, including extubation, was exemplary and outpatient strategies were prudent. Furthermore, the author presents an outstanding review of literature and a thoughtful discussion.
Although the patient was fortunate to survive, she is still left with debilitating left ventricular (LV) impairment that is unlikely to improve further. Clearly, a prompt and early diagnosis of AMI from the first ECG performed by the primary physician would have hastened care and may have contributed to greater LV salvage. Acceptance of this case study will hopefully lead to dissemination of the importance of early recognition of this entity.
- Pretty HC. Dissecting aneurysm of coronary artery in a woman aged 42: rupture. Br Med J. 1931; 1: 667.
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- De Maio SJ Jr, Kinsella SH, Silverman ME. Clinical course and long-term prognosis of spontaneous coronary artery dissection. Am J Cardiol. 1989; 64: 471-474.
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- Koul AK, Hollander G, Moskovits N, Frankel R, Herrera L, Shani J. Coronary artery dissection during pregnancy and the postpartum period: two cases and review of the literature. Catheter Cardiovasc Interv. 2001; 52: 88-94.
- Asuncion CM, Hyun J. Dissecting intramural hematoma of the coronary artery in pregnancy and the puerperium. Obstet Gynecol. 1972; 40: 202-210.
- Heefner WA. Dissecting hematoma of the coronary artery. A possible complication of oral contraceptive therapy. JAMA. 1973; 223: 550-551.
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- Cheung S, Mithani V, Watson RM. Healing of spontaneous coronary dissection in the context of glycoprotein IIB/IIIA inhibitor therapy: a case report. Catheter Cardiovasc Interv. 2000; 51: 95-100.
- Dhawan R, Singh G, Fesniak H. Spontaneous coronary artery dissection: the clinical spectrum. Angiology. 2002; 53: 89-93.
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- Adès LC, Waltham RD, Chiodo AA, Bateman JF. Myocardial infarction resulting from coronary artery dissection in an adolescent with Ehlers-Danlos syndrome type IV due to a type III collagen mutation. Br Heart J. 1995; 74: 112-116.
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