Spontaneous coronary artery dissection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Nate Michalak, B.A. Arzu Kalayci, M.D. [3]

Synonyms and keywords: SCAD

Spontaneous coronary artery dissection (SCAD) is a rare but under recognized cause of acute coronary syndrome and sudden cardiac death, which predominantly affects young, healthy women with few or no traditional cardiovascular risk factors.Spontaneous coronary artery dissection (SCAD) was first described by Pretty in 1931 in which a 42-year-old woman presented with nausea and chest pain died unexpectedly due to rupture of a dissecting atheromatous aneurysm in the right coronary artery following repetitive retching and vomiting. In the post-morterm examination, heart muscle and valve appeared normal, and there was extensive hemorrhage between aorta and pulmonary artery secondary to coronary artery rupture presumably during the sudden and violent retching attack. Spontaneous coronary artery dissection can be classified based on angiographic appearance into type 1 (evident arterial wall stain with multiple radiolucent lumens), type 2 (diffuse smooth stenosis of varying severity), and type 3 lesions (focal or tubular stenosis mimicking atherosclerosis). At present, the pathophysiology of non-atherosclerotic spontaneous coronary artery dissection (NA-SCAD) continues to be poorly understood due to the rarity of this condition and its heterogeneous pathology. Although intimal tear or bleeding of vasa vasorum with intermedial hemorrhage seems to be the most probable reason, the exact underlying mechanism is still unknown.The exact etiology of spontaneous coronary artery dissection remains elusive; however, fibromuscular dysplasia and takotsubo cardiomyopathy have been considered as the potential cause of spontaneous coronary artery dissection. The underlying causes associated with SCAD include emotional stress, physical stress such as extreme valsalva maneuver, retching, vomiting, coughing, isometric exercise, history of using stimulant medications or illicit drugs, pregnancy, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease, celiac disease, vascular Ehlers–Danlos syndrome, Marfan’s syndrome, Loeys–Dietz syndrome. Spontaneous coronary artery dissection should be differentiated from other causes of acute coronary syndrome. Features suggestive of spontaneous coronary artery dissection include myocardial infarction in young women (age ≤50), absence of traditional cardiovascular risk factors, little or no evidence of coronary atherosclerosis, peripartum state, history of fibromuscular dysplasia, and history of connective tissue disorder or systemic inflammatory disorder.The annual incidence of spontaneous coronary artery dissection is estimated at 0.26 per 100,000 persons (0.33 in women and 0.18 in men), corresponding to approximately 800 new cases per year in the United States. The true prevalence of spontaneous coronary artery dissection in the general population remains unknown; however, retrospective angiographic registries have reported a SCAD detection rate of 0.1 to 1.1% among all coronary angiograms performed.The risk factors for spontaneous coronary artery dissection include predisposing factors ( vasculopathy, pregnancy, connective tissue disorder, systemic inflammation) and precipitating stressors (e.g., strenuous exercise, emotional stress, recreational drugs).Features that raise the index of suspicion for SCAD include myocardial infarction in young women (age ≤50), absence of traditional cardiovascular risk factors, little or no evidence of coronary atherosclerosis, peripartum state, history of fibromuscular dysplasia, history of connective tissue disorder or systemic inflammation. SCAD usually is the result of an underlying vascular or connective tissue disorders. In order to provide the best care to patients with SCAD, the scientific statement from the American Heart Association (AHA) recommended a detailed review of systems and personal and family history of SCAD-associated symptoms and conditions. In addition, AHA scientific statement recommended a complete vascular exam. Routine clinical or genetic screening of asymptomatic relatives of patients with SCAD is not recommended. However, genetic screening is recommended in first-degree family members of patients with SCAD in whom a monogenic vascular disease has been identified.The natural history of spontaneous coronary artery dissection has not been well characterized. Early reports based on post-mortem examinations after sudden cardiac death suggest a dismal prognosis. However, recent studies demonstrate that most patients survive initial hospitalization and have a favorable prognosis following clinical stabilization.Coronary angiography is the standard for diagnosing spontaneous coronary artery dissection. Adjunctive imaging modalities such as intravascular ultrasonography (IVUS), optical coherence tomography (OCT), computed tomography angiography (CTA), and magnetic resonance angiography (MRA) may offer complementary details for establishing a definitive diagnosis.The hallmark symptom of spontaneous coronary artery dissection (SCAD) is angina pectoris, similar to other acute coronary syndromes, which may radiate to the jaw or left arm. SCAD should be suspected with these symptoms in relatively young women, especially those in postpartum status. However, many patients do not have typical risk factors of coronary artery disease. Patients are typically asymptomatic on follow-up.Physical exam in SCAD may include tachycardia, bradycardia, hypertension, hypotension, rale, syncope based on the the coronary arteries involvement and ventricular dysfunction.Laboratory findings consistent with the diagnosis of spontaneous coronary artery dissection is similar to myocardial infarction as it most commonly presents with this manifestation. It includes elevated levels of troponin which may be absent in 27% of the patients.Electrocardiogram findings vary according to the coronary flow-limitation by the dissection flap or intramural hematoma. There can be no changes in ECG in some cases. In other cases ECG may show any of changes.The current gold standard for diagnosing spontaneous coronary artery dissection (SCAD) is coronary angiography, as it is widely available and the first-line imaging modality for patients presenting with the acute coronary syndrome. The predominant angiographic feature of SCAD consists of diffuse smooth narrowing of varying severity involving mid-to-distal coronary segments, secondary to compression of the true lumen and/or expansion of the false lumen by the development of an intramural hematoma. The typical appearance of extraluminal contrast staining, multiple radiolucent lumens, spiral dissection, or intraluminal filling defects is less commonly observed. Other angiographic findings associated with SCAD include coronary tortuosity, myocardial bridging, and coronary fibromuscular dysplasia.coronary computed tomography angiography maybe helpful in the diagnosis of spontaneous coronary artery dissection. Findings on coronary computed tomography angiography suggestive of spontaneous coronary artery dissection include abrupt luminal stenosis of the coronary lumen, intramural hematoma,tapered luminal stenosis, epicardial fat strand, coronary tortuosity, coronary bridging, myocardial hypoperfusion, regional wall motion abnormality.Cardiac magnetic resonance (CMR) is a valuable tool for diagnosis of spontaneose coronary artery dissection (SCAD) in patients as follows: pregnant women for avoiding radiation of coronary angiography, unclear evidence of acute coronary syndrome during coronary angiography, differentiating of SCAD from myocarditis, takotsubo cardiomyopathy. Findings of CMR associated with SCAD include evidence of myocardial infarction with subendocardial LGE,microvascular obstruction, myocardial edema.Echocardiography is helpful in the assessment of regional wall motion abnormalities, chamber size, and diastolic function and monitoring of ventricular recovery after SCAD. Contrast and strain echocardiography may be useful for evaluation of underlying perfusion and myocardial dysfunction in SCAD.When the diagnosis of spontaneous coronary artery dissection (SCAD) cannot be ascertained by the standard coronary angiography, intracoronary imaging such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT) may provide complementary information for establishing a definitive diagnosis. Coronary computed tomography angiography (CCTA) may be useful for non-invasive follow-up of SCAD involving proximal or large-caliber coronary arteries. OCT findings suggestive of SCAD may include the presence of two lumens and intramural hematoma.Long-term treatment for spontaneous coronary artery dissection pursues several main goals including antianginal therapy, prevention of recurrence, assessment, and management of extra coronary vascular abnormalities, and improvement of quality of life. Acute management of myocardial infarction in SCAD is medical therapy in approximately 80% of the patients. Myocardial infarction in the context of SCAD is different from the myocardial infarction in the context of atherosclerosis and therefore makes it unfavorable for revascularization approaches.There are no specific guidelines regarding the optimal management of spontaneous coronary artery dissection. Based on the clinical and angiographic scenario, treatment options include conservative medical regimens similar to that for acute coronary syndrome, percutaneous coronary intervention, and/or coronary artery bypass surgery. In the majority of cases, SCAD may be managed successfully with medical treatment alone in the absence of ongoing myocardial ischemia or hemodynamic instability. Initial conservative management typically includes antithrombotic therapy with heparin, aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitors, and antiischemic therapy with beta blockers and nitrates. However, the use of antithrombotic therapy may increase the risk of bleeding in the false lumen causing an expansion of the intramural hematoma, resulting in a decreased flow through the true lumen.Fibrinolytics should be avoided. Calcium channel blockers may offer relief in coronary artery spasm.Conservative management should be the first choice if emergent revascularization is not necessary. However, optimal management is in question due to insufficient clinical experience. There are some treatment options including conservative management, emergency revascularization (PCI or CABG), fibrinolytic therapy, mechanical hemodynamic support, and even cardiac transplantation have been reported.The preference of the approach should be tailored to the patient’s clinical status.Coronary artery bypass graft (CABG) is an important reperfusion therapy in a selected group of SCAD patients and also a rescue strategy in the management of failed PCI.Indications for surgical revascularization include multivessel involvement, Left main coronary artery involvement, progression/worsening of dissection, significant narrowing of the arterial lumen, refractory or recurrent myocardial ischemia. In the event of severe refractory heart failure, heart transplantation may be considered. There is no established primary prevention measurement for spontaneous coronary artery dissection.Secondary prevention strategies following spontaneous coronary artery dissection include avoidance of extreme isometric or competitive physical exercise and also psychosocial support.Future studies are needed to further elucidate the underlying pathophysiology of this complex disorder as well as to gain a better understanding of the optimal treatment strategies and long-term outcomes of this unique patient population.

Spontaneous coronary artery dissection (SCAD) was first described by Pretty in 1931 in which a 42-year-old woman presented with nausea and chest pain died unexpectedly due to rupture of a dissecting atheromatous aneurysm in the right coronary artery following repetitive retching and vomiting. In the post-morterm examination, heart muscle and valve appeared normal, and there was extensive hemorrhage between aorta and pulmonary artery secondary to coronary artery rupture presumably during the sudden and violent retching attack.

Spontaneous coronary artery dissection can be classified based on angiographic appearance into type 1 (evident arterial wall stain with multiple radiolucent lumens), type 2 (diffuse smooth stenosis of varying severity), and type 3 lesions (focal or tubular stenosis mimicking atherosclerosis). Type 4 SCAD lesion is characterized by dissection leading to an abrupt total occlusion, usually of a distal coronary segment. The total occlusion occurs as a result of diminished true lumen due to external compression by intraluminal hematoma rather than embolism. The intermediate type 1/2 SCAD lesion is characterized by the appearance of type 1 in conjunction with type 2 lesion.

At present, the pathophysiology of non-atherosclerotic spontaneous coronary artery dissection (NA-SCAD) continues to be poorly understood due to the rarity of this condition and its heterogeneous pathology. Although intimal tear or bleeding of vasa vasorum with intermedial hemorrhage seems to be the most probable reason, the exact underlying mechanism is still unknown. In a SCAD registry, a total of 5% to 8% of patients were carriers of genetic mutations for connective tissue disorders. SCAD may also be associated with a variety of disorders including but not limited to fibromuscular dysplasia, Connective tissue disorders, and autoimmune diseases such as systemic lupus erythematous.

The exact etiology of spontaneous coronary artery dissection remains elusive; however, fibromuscular dysplasia and takotsubo cardiomyopathy have been considered as the potential cause of spontaneous coronary artery dissection. The underlying causes associated with SCAD include emotional stress, physical stress such as extreme valsalva maneuver, retching, vomiting, coughing, isometric exercise, history of using stimulant medications or illicit drugs, pregnancy, and connective tissue disorders.

Spontaneous coronary artery dissection should be differentiated from other causes of acute coronary syndrome. Features suggestive of spontaneous coronary artery dissection include myocardial infarction in young women (age ≤50), absence of traditional cardiovascular risk factors, little or no evidence of coronary atherosclerosis, peripartum state, history of fibromuscular dysplasia, and history of connective tissue disorder or systemic inflammatory disorder.

The annual incidence of spontaneous coronary artery dissection is estimated at 0.26 per 100,000 persons (0.33 in women and 0.18 in men), corresponding to approximately 800 new cases per year in the United States. The true prevalence of spontaneous coronary artery dissection in the general population remains unknown; however, retrospective angiographic registries have reported a SCAD detection rate of 0.1% to 1.1% among all coronary angiograms performed. The case fatality rate of SCAD is relatively low compared with other causes of ACS, with an estimated in-hospital mortality rate of 0 to 4%. The average age at diagnosis of SCAD in females ranges from 44 to 53 years, although patients may present with SCAD in their second through ninth decades of life. SCAD has a strong predilection for young women with no or minimal traditional cardiovascular risk factors. It has been reported in all major racial and ethnic groups, with the majority of patients being white.

The risk factors for spontaneous coronary artery dissection include predisposing factors ( vasculopathy, pregnancy, connective tissue disorder, systemic inflammation) and precipitating stressors (e.g., strenuous exercise, emotional stress, recreational drugs).Features that raise the index of suspicion for SCAD include myocardial infarction in young women (age ≤50), absence of traditional cardiovascular risk factors, little or no evidence of coronary atherosclerosis, peripartum state, history of fibromuscular dysplasia, history of connective tissue disorder or systemic inflammation.

SCAD usually is the result of an underlying vascular or connective tissue disorders. In order to provide the best care to patients with SCAD, the scientific statement from the American Heart Association (AHA) recommended a detailed review of systems and personal and family history of SCAD-associated symptoms and conditions. In addition, AHA scientific statement recommended a complete vascular exam. Routine clinical or genetic screening of asymptomatic relatives of patients with SCAD is not recommended. However, genetic screening is recommended in first-degree family members of patients with SCAD in whom a monogenic vascular disease has been identified.

The natural history of spontaneous coronary artery dissection has not been well characterized. Early reports based on post-mortem examinations after sudden cardiac death suggest a dismal prognosis. However, recent studies demonstrate that the majority of patients survive initial hospitalization and have a favorable prognosis following clinical stabilization. Some of the complications of SCAD include extension of dissection, recurrence of dissection, myocardial stunning, myocardial infarction, congestive heart failure, cardiogenic shock, ventricular arrhythmia, and sudden cardiac death.

Coronary angiography is the standard for diagnosing spontaneous coronary artery dissection. Adjunctive imaging modalities such as intravascular ultrasonography (IVUS), optical coherence tomography (OCT), computed tomography angiography (CTA), and magnetic resonance angiography (MRA) may offer complementary details for establishing a definitive diagnosis.

The hallmark symptom of spontaneous coronary artery dissection (SCAD) is angina pectoris, similar to other acute coronary syndromes, which may radiate to the jaw or left arm. SCAD should be suspected with these symptoms in relatively young women, especially those in postpartum status. However, many patients do not have typical risk factors of coronary artery disease. Patients are typically asymptomatic on follow-up.

Physical exam in SCAD may include tachycardia, bradycardia, hypertension, hypotension, rale, syncope based on the the coronary arteries involvement and presence of ventricular dysfunction.

Laboratory findings consistent with the diagnosis of spontaneous coronary artery dissection is similar to myocardial infarction as it most commonly presents with this manifestation. It includes elevated levels of troponin which may be absent in 27% of the patients.

Electrocardiogram findings vary according to the coronary flow-limitation by the dissection flap or intramural hematoma. There can be no changes in ECG in some cases. In other cases ECG may show any of changes.

The current gold standard for diagnosing spontaneous coronary artery dissection (SCAD) is coronary angiography, as it is widely available and the first-line imaging modality for patients presenting with the acute coronary syndrome. The predominant angiographic feature of SCAD consists of diffuse smooth narrowing of varying severity involving mid-to-distal coronary segments, secondary to compression of the true lumen and/or expansion of the false lumen by the development of an intramural hematoma. The typical appearance of extraluminal contrast staining, multiple radiolucent lumens, spiral dissection, or intraluminal filling defects is less commonly observed. Other angiographic findings associated with SCAD include coronary tortuosity, myocardial bridging, and coronary fibromuscular dysplasia.

coronary computed tomography angiography maybe helpful in the diagnosis of spontaneous coronary artery dissection. Findings on coronary computed tomography angiography suggestive of spontaneous coronary artery dissection include abrupt luminal stenosis of the coronary lumen, intramural hematoma,tapered luminal stenosis, epicardial fat strand, coronary tortuosity, coronary bridging, myocardial hypoperfusion, regional wall motion abnormality.

Cardiac magnetic resonance (CMR) is a valuable tool for diagnosis of spontaneose coronary artery dissection (SCAD) in patients as follows: pregnant women for avoiding radiation of coronary angiography, unclear evidence of acute coronary syndrome during coronary angiography, differentiating of SCAD from myocarditis, takotsubo cardiomyopathy. Findings of CMR associated with SCAD include evidence of myocardial infarction with subendocardial late gadolinium enhancement, microvascular obstruction, myocardial edema.

Echocardiography is helpful in the assessment of regional wall motion abnormalities, chamber size, and diastolic function and monitoring of ventricular recovery after SCAD. Contrast and strain echocardiography may be useful for evaluation of underlying perfusion and myocardial dysfunction in SCAD.

When the diagnosis of spontaneous coronary artery dissection (SCAD) cannot be ascertained by the standard coronary angiography, intracoronary imaging such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT) may provide complementary information for establishing a definitive diagnosis. Coronary computed tomography angiography (CCTA) may be useful for non-invasive follow-up of SCAD involving proximal or large-caliber coronary arteries. OCT findings suggestive of SCAD may include the presence of two lumens and intramural hematoma.

Acute management of myocardial infarction in SCAD is medical therapy in approximately 80% of the patients. Myocardial infarction in the context of SCAD is different from the myocardial infarction in the context of atherosclerosis and therefore makes it unfavorable for revascularization approaches. Long-term treatment for spontaneous coronary artery dissection pursues several main goals including antianginal therapy, prevention of recurrence, assessment, and management of extra coronary vascular abnormalities, and improvement of quality of life. To improve the qualityof life in patients with SCAD, consider cardiac rehabilitation referral and manage patients comorbidities.

There are no specific guidelines regarding the optimal management of spontaneous coronary artery dissection. Based on the clinical and angiographic scenario, treatment options include conservative medical regimens similar to that for acute coronary syndrome, percutaneous coronary intervention, and/or coronary artery bypass surgery. In the majority of cases, SCAD may be managed successfully with medical treatment alone in the absence of ongoing myocardial ischemia or hemodynamic instability. Initial conservative management typically includes antithrombotic therapy with heparin, aspirin, clopidogrel and glycoprotein IIb/IIIa inhibitors, and antiischemic therapy with beta blockers and nitrates. However, the use of antithrombotic therapy may increase the risk of bleeding in the false lumen causing an expansion of the intramural hematoma, resulting in a decreased flow through the true lumen.Fibrinolytics should be avoided. Calcium channel blockers may offer relief in coronary artery spasm.

Conservative management should be the first choice if emergent revascularization is not necessary. However, optimal management is in question due to insufficient clinical experience. There are some treatment options including conservative management, emergency revascularization (PCI or CABG), fibrinolytic therapy, mechanical hemodynamic support, and even cardiac transplantation.The preference of the approach should be tailored to the patient’s clinical status.

Coronary artery bypass graft (CABG) is an important reperfusion therapy in a selected group of SCAD patients and also a rescue strategy in the management of failed PCI.Indications for surgical revascularization include multivessel involvement, Left main coronary artery involvement, progression/worsening of dissection , significant narrowing of the arterial lumen, refractory or recurrent myocardial ischemia. In the event of severe refractory heart failure, heart transplantation may be considered.

There is no established primary prevention measurement for spontaneous coronary artery dissection.

Secondary prevention strategies following spontaneous coronary artery dissection include avoidance of extreme isometric or competitive physical exercise and also psychosocial support.

Future studies are needed to further elucidate the underlying pathophysiology of this complex disorder as well as to gain a better understanding of the optimal treatment strategies and long-term outcomes of this unique patient population.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nate Michalak, B.A.; Arzu Kalayci, M.D. [2]

Synonyms and keywords: SCAD

The first case of spontaneous coronary artery dissection was described by Pretty in 1931. In the post-morterm examination, heart muscle and valve appeared normal, and there was extensive hemorrhage between aorta and pulmonary artery secondary to coronary artery rupture presumably during the sudden and violent retching attack.

• Spontaneous coronary artery dissection (SCAD) was first described by Pretty in 1931 in which a 42-year-old woman presented with nausea and chest pain died unexpectedly due to rupture of a dissecting atheromatous aneurysm in the right coronary artery following repetitive retching and vomiting.
• In the post-morterm examination, heart muscle and valve appeared normal, and there was extensive hemorrhage between aorta and pulmonary artery secondary to coronary artery rupture presumably during the sudden and violent retching attack.^[1]
• Since then, more than 1,500 cases of SCAD have been reported in the English literature.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nate Michalak, B.A.; Arzu Kalayci, M.D. [2]

Synonyms and keywords: SCAD

Spontaneous coronary artery dissection can be classified based on angiographic appearance into type 1 (evident arterial wall stain with multiple radiolucent lumens), type 2 (diffuse smooth stenosis of varying severity), and type 3 lesions (focal or tubular stenosis mimicking atherosclerosis). Type 4 SCAD lesion is characterized by dissection leading to an abrupt total occlusion, usually of a distal coronary segment. The total occlusion occurs as a result of diminished true lumen due to external compression by intraluminal hematoma rather than embolism. The intermediate type 1/2 SCAD lesion is characterized by the appearance of type 1 in conjunction with type 2 lesion.

The National Heart, Lung, and Blood Institute (NHLBI) classification scheme for coronary dissection was devised in the pre-stent era for classifying the dissection following balloon angioplasty (i.e., iatrogenic dissection). In light of the distinctive angiographic features of spontaneous coronary artery dissection (SCAD), Saw et al. proposed a classification system to better characterize the lesions:^{[1][2][3][4][5]}

Type 1 SCAD lesion is characterized by the pathognomonic appearance of contrast dye staining of the arterial wall with multiple radiolucent lumens, with or without the presence of dye hang-up or slow contrast clearing from the lumen.

Projection angle: 14 RAO, 35 CRA. Type 1 SCAD is seen in OM2.

Type 2 SCAD lesion is characterized by diffuse (typically >20–30 mm) and usually smooth narrowing that can vary in severity from inconspicuous mild stenosis to complete occlusion, plus:

a. no response to intracoronary nitroglycerin and no atherosclerotic lesions in other coronary arteries

OR

b. repeat coronary angiogram showing angiographic resolution of the dissected segment or previous angiogram showing normal artery

OR

c. intracoronary imaging with optical coherence tomography or intravascular ultrasound proving the presence of intramural hematoma (IMH) and double-lumen

Type 2 SCAD lesion commonly involves the mid to distal segments of coronary arteries and can be so extensive that it affects the distal tip. Accordingly, type 2 lesions can be further divided into two variants (type 2 variant A and variant B).

In type 2 variant A lesion, the coronary segments proximal and distal to dissection are normal.

Projection angle: 25 LAO, 20 CRA. Type 2A SCAD is seen in R3, R4.

In type 2 variant B lesion, the dissection extends to the apical tip of the artery without discernible normal segment distally.

Projection angle: 41 RAO, 19 CRA. Type 2B SCAD is seen starting in L2 resulting in a total occlusion.

Type 3 SCAD lesion is characterized by focal or tubular (typically <20 mm) stenosis that mimics atherosclerosis, which requires intracoronary imaging (e.g. optical coherence tomography or intravascular ultrasound) to prove the presence of intramural hematoma or double-lumen. Angiographic features that may be useful in differentiating type 3 SCAD lesion from atherosclerosis include:

a. lack of atherosclerotic changes in other coronary arteries

b. long lesions (11–20 mm)

c. hazy stenosis

d. linear stenosis

Projection angle: 1 LAO, 35 CRA. Type 3 SCAD is seen in D1.

Type 4 SCAD lesion is characterized by dissection leading to an abrupt total occlusion, usually of a distal coronary segment. The total occlusion occurs as a result of diminished true lumen due to external compression by intraluminal hematoma rather than embolism. In keeping with the natural history of SCAD, spontaneous healing may be evident on subsequent angiography.

The intermediate type 1/2 SCAD lesion is characterized by the appearance of type 1 in conjunction with type 2 lesion. Diffuse, smooth narrowing of the vessel (suggestive of type 2 lesion) adjacent to multiple radiolucent lumens with arterial wall staining (suggestive of a type 1 lesion) is observed.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Arzu Kalayci, M.D. [2]; Nate Michalak, B.A.

Synonyms and keywords: SCAD

At present, the pathophysiology of non-atherosclerotic spontaneous coronary artery dissection (NA-SCAD) continues to be poorly understood due to the rarity of this condition and its heterogeneous pathology. Although intimal tear or bleeding of vasa vasorum with intermedial hemorrhage seems to be the most probable reason, the exact underlying mechanism is still unknown. In a SCAD registry, a total of 5% to 8% of patients were carriers of genetic mutations for connective tissue disorders. SCAD may also be associated with a variety of disorders including but not limited to fibromuscular dysplasia, Connective tissue disorders, and autoimmune diseases such as systemic lupus erythematous.

• NA-SCAD can develop in any layer (intima , media, or adventitia) of the coronary artery wall.
• The initiation and the pattern of dissection in NA-SCAD is different from the pattern observed in patients with pre-existing atherosclerosis.
• The plane of dissection mostly occurs within the outer third of the tunica media or between the media and adventitia in NA-SCAD.
• Dissections can be present within either one artery or several arteries concomitantly in this state.^[1][2]

Two possible mechanisms have been described for the arterial wall separation: ^[3]

• The first one is intimal tear hypothesis, in which intramural blood accumulation may develop through a primary entry tear which occurs due to the damaged intimal surface and causes separation of the arterial wall.
• The second one is, medial haemorrhage hypothesis, in which spontaneous rupture of newly formed vasa vasorum in response to injury can cause a haemorrhage within between the arterial wall layers.
• Both of them result in a creation of false lumen filled with intramural haematoma. ^[4]
• High pressure of the hematoma within the arterial wall may lead to a rupture through the intima and create a “reverse” intimal rupture.
• Furthermore, increasing pressure of enlarging haematoma in the false lumen may also lead to luminal compression and precipitate myocardial ischemia and infarction. Thrombus can occur in both true and false lumen.
• Thrombosis of the true lumen mostly originates from intimal rupture sites.
• The current literature remains controversial regarding whether there is a thrombosis in the true lumen in patients with NA-SCAD.
• Two angiographic and one optical coherence tomography (OCT) studies have proposed that there was no thrombus in the arterial true lumen. ^{[5] [6] [7]}
• Another OCT study has detected some insignificant thrombosis in the false and also true lumen.^[8]
• Atherosclerotic variant of SCAD has basically different characteristic which only includes medial atrophy and scarring. ^[9]
• Unlike the atherosclerotic pattern, NA-SCAD can have an expanded dissection particularly in the presence of an underlying arteriopathy which makes the arterial wall more fragile.
• Intracoronary imaging studies showed that NA-SCAD cases have a normal intimal structure. ^{[7] [8]}
• Pregnancy is a significant risk factor for NA-SCAD.
• Some negative effects of hormones and elevated hemodynamic stress make the coronary arterial wall weak during pregnancy.^[10]
• Multiparty causes a longer exposure to pregnancy-associated changes which result in an increased risk of SCAD.^[11] Histological analyses revealed a periarteritis including eosinophilic infiltrates in the tunica adventitia that may lead to a separation of the arterial wall layers resulting in dissection.
• On the other hand this inflammatory state could be a response to the dissection instead of being an underlying mechanism. ^[8]
• A retrospective study has shown the relationship between coronary artery tortuosity and SCAD. ^[12].
• An association has been described between coronary tortuosity and fibromuscular dysplasia.
• Tortuosity is a consequence of an underlying vasculopathy likewise dissection. ^{[13] [3]}

• In a SCAD registry, a total of 5% to 8% of patients with SCAD were carriers of genetic mutations for connective tissue disorders.
  
• Genes involved in the pathogenesis of SCAD include but not limited to:
  
• COL3A1 ^[15]
• FBN1 ^[16]
• COL4A5 ^[15]
• PKD1 ^[17][18]
• PKD2 ^[17]
• SMAD3 ^[19][20]
• COL1A1 ^[15]
• COL1A2 ^[15]

Conditions associated with SCAD include:

• Connective tissue disorders such as: ^[21]
  • Vascular Ehlers–Danlos syndrome
  • Marfan’s syndrome
  • Loeys–Dietz syndrome
• Pregnancy ^[22]
• Fibromuscular dysplasia ^[23]
  • In a prospective cohort of SCAD patients, approximately 50% demonstrated the evidence of fibromuscular dysplasia.^[24]
• Inflammatory disorders such as:
  • Systemic lupus erythematosus ^[25]
  • Sarcoidosis ^[26]
  • Celiac disease ^[27]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Nate Michalak, B.A. Arzu Kalayci, M.D. [3]

Synonyms and keywords: SCAD

The exact etiology of spontaneous coronary artery dissection remains elusive; however, fibromuscular dysplasia and takotsubo cardiomyopathy have been considered as the potential cause of spontaneous coronary artery dissection. The underlying causes associated with SCAD include emotional stress, physical stress such as extreme valsalva maneuver, retching, vomiting, coughing, isometric exercise, history of using stimulant medications or illicit drugs, pregnancy, and connective tissue disorders.

Common causes associated with spontaneous coronary artery dissection (SCAD) include:^[1][2]

• Emotional stress
• Physical stress such as extreme valsalva maneuver, retching, vomiting, coughing, isometric exercise
• Using stimulant medications, illicit drugs
• Hormonal triggers such as pregnancy
• Inflammatory disorders such as systemic lupus erythematosus, sarcoidosis, Crohn’s disease, Ulcerative colitis , celiac disease, fibromuscular dysplasia (FMD), takotsubo cardiomyopathy (TCM)
• Connective tissue disorders such as vascular Ehlers–Danlos syndrome, marfan’s syndrome, Loeys–Dietz syndrome, cystic medial necrosis, systemic lupus erythematosus, polyarteritis nodosa, sarcoidosis, churg-Strauss syndrome, wegener’s granulomatosis, rheumatoid arthritis, giant cell arthritis

• FMD is a non-atherosclerotic vasculopathy characterized by thickening, fibrosis, and disarray of the arterial wall that primarily affects small and medium-sized vessels.
• The association between FMD and SCAD has been well described,^[3][4][5][6]
• The biological proof of causation has been supported by histopathologic reports.^[7][8][9]
• The presence of FMD may weaken the artery architecture and lead to aneurysm formation or coronary dissection.^[10]

• Both TCM and SCAD affect predominantly women and may be precipitated by emotional stress or strenuous exercise associated with sympathetic discharge.
• Numerous reports have described the concurrence of TCM and SCAD.^{[11][12][13][14][15]}
• In the setting of TCM, vigorous contraction of the left ventricular base in conjunction with the adjacent akinetic/dyskinetic segments could form a prerequisite anatomic/functional substrate for the causation of SCAD.^[16]
• The coronary dissection plane may develop as a result of excessive movement of the epicardial vessels and increased shear stress on the vessel wall at the hinge point between the hyperdynamic and dyskinetic/akinetic myocardium.^[17]
• The coronary arteries traversing the anterior or anterolateral wall would be more vulnerable to dissection as this region marks the transition point of the hyperdynamic basal segment and the remaining dyskinetic/akinetic left ventricular segments.
• Another plausible mechanism is that elevated catecholamine concentrations in TCM may cause epicardial coronary vasoconstriction and/or spasm, which in turn leads to increased arterial shear stress and subsequent intimal tear or disruption of vasa vasorum.^[18]
• The post-ischemic myocardial stunning associated with SCAD could lead to TCM,^[12], thus forming the “TCM begets SCAD, and SCAD begets TCM” vicious cycle.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Arzu Kalayci, M.D. [3]

Synonyms and keywords: SCAD

Spontaneous coronary artery dissection should be differentiated from other causes of acute coronary syndrome. Features suggestive of spontaneous coronary artery dissection include myocardial infarction in young women (age ≤50), absence of traditional cardiovascular risk factors, little or no evidence of coronary atherosclerosis, peripartum state, history of fibromuscular dysplasia, and history of connective tissue disorder or systemic inflammatory disorder.

Albeit an infrequent condition, spontaneous coronary artery dissection (SCAD) should be included in the differential diagnosis of acute coronary syndrome, particularly among young women with risk factors such as vasculopathy, pregnancy, connective tissue disorder, systemic inflammation, strenuous exercise, emotional stress, or recreational drug use. While demographic and angiographic characteristics may be useful in differentiating SCAD from other causes of myocardial ischemia, intracoronary imaging such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) may be required for establishing a definitive diagnosis.

^{[1][2][3][4][5][6][7][8][9][10][11]}

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nate Michalak, B.A. Arzu Kalayci, M.D. [2]

Synonyms and keywords: SCAD

The annual incidence of spontaneous coronary artery dissection is estimated at 0.26 per 100,000 persons (0.33 in women and 0.18 in men), corresponding to approximately 800 new cases per year in the United States. The true prevalence of spontaneous coronary artery dissection in the general population remains unknown; however, retrospective angiographic registries have reported a SCAD detection rate of 0.1 to 1.1% among all coronary angiograms performed. The case fatality rate of SCAD is relatively low compared with other causes of ACS, with an estimated in-hospital mortality rate of 0 to 4%. The average age at diagnosis of SCAD in females ranges from 44 to 53 years, although patients may present with SCAD in their second through ninth decades of life. SCAD has a strong predilection for young women with no or minimal traditional cardiovascular risk factors. It has been reported in all major racial and ethnic groups, with the majority of patients being white.

• The true prevalence of spontaneous coronary artery dissection (SCAD) remains unknown because it is an under-diagnosed condition.
• Missed diagnoses may be driven by a low suspicion of acute coronary syndrome (ACS) in young female even in the presence of classic manifestations, limitations of current coronary angiographic techniques, and lack of clinician familiarity with the condition.^[1]

• The prevalence of SCAD reported by retrospective angiographic registries ranges from 0.2 to 2.0% among all ACS cases and from 8.7 to 35.0% among women < 50 years with ACS.^{[2][3][4][5][6][7][8][9]}

• The annual incidence of SCAD is estimated at 0.26 per 100,000 persons (0.33 in women and 0.18 in men), corresponding to approximately 800 new cases per year in the United States.^[10]

• The case fatality rate of SCAD is relatively low compared with other causes of ACS, with an estimated in-hospital mortality rate of 0 to 4%.^[2]

• The average age at diagnosis of SCAD in females ranges from 44 to 53 years, although patients may present with SCAD in their second through ninth decades of life.^[1][11]

• The prevalence of SCAD decreases with age, and is estimated at 7.6%, 4.0%, 2.1%, and 1.2% in women below the age of 40, 50, 60, and 70, respectively.^[2]

• SCAD has a strong predilection for young women with no or minimal traditional cardiovascular risk factors.
• SCAD is one of the most common non-atherosclerotic coronary artery diseases in women <50 years of age and accounts for one-fourth of myocardial infarctions.^[12]
• The risk of SCAD has been associated with pregnancy as well as the use of oral contraceptives.^[13][14][15]
• Possible mechanisms underlying increased prevalence of SCAD in this population include structural alterations in the arterial wall secondary to hormonal change, increased shear stress during labor, fragmentation of reticulin fibers, loosening of ground substance, and hypertrophy of smooth muscle.^[16]

• SCAD has been reported in all major racial and ethnic groups, with the majority of patients being white. ^[8][17][18]
• This finding may have been influenced by referral and sampling bias as well as the demography of patients from the reporting hospitals.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Zand, M.D.[2] Nate Michalak, B.A. Arzu Kalayci, M.D. [3]

Synonyms and keywords: SCAD

The risk factors for spontaneous coronary artery dissection include predisposing factors ( vasculopathy, pregnancy, connective tissue disorder, systemic inflammation) and precipitating stressors (e.g., strenuous exercise, emotional stress, recreational drugs).Features that raise the index of suspicion for SCAD include myocardial infarction in young women (age ≤50), absence of traditional cardiovascular risk factors, little or no evidence of coronary atherosclerosis, peripartum state, history of fibromuscular dysplasia, history of connective tissue disorder or systemic inflammation.

• The phenotypic manifestation of spontaneous coronary artery dissection (SCAD) may occur as a result of predisposing factors compounded by precipitating stressors.^[1]
• The presence of either predisposing or precipitating factors increases the risk of developing a dissection.
• The potential risk factors for SCAD include:^[2][3][4]

• After adjusting for cardiovascular risk factors, predisposing arteriopathies, precipitating stressors, medications, and revascularization, hypertension increased the risk of SCAD recurrence by 2.5 times, whereas beta-blocker usage reduced the recurrence risk by 64%.^[5]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]

Synonyms and keywords: SCAD

SCAD usually is the result of an underlying vascular or connective tissue disorders. In order to provide the best care to patients with SCAD, the scientific statement from the American Heart Association (AHA) recommends a detailed review of systems and personal and family history of SCAD-associated symptoms and conditions. In addition, the AHA statement recommends a complete vascular exam. Routine clinical or genetic screening of asymptomatic relatives of patients with SCAD is not recommended. However, genetic screening is recommended in first-degree family members of patients with SCAD in whom a monogenic vascular disease has been identified.

SCAD usually is the result of an underlying vascular or connective tissue disorders. In order to provide the best care to patients with SCAD, the scientific statement from the American Heart Association (AHA) recommends a detailed review of systems and personal and family history of SCAD-associated symptoms and conditions. ^[1]
In addition, the AHA statement recommends a complete vascular exam with palpation and auscultation of the following arteries:

• Abdominal aorta
• Cervical carotid arteries
• Peripheral arteries of the upper and lower extremities

The AHA statement recommends a list of questions to rule out SCAD-associated vasculopathy and connective tissue disorders: ^[1]

• Genetic screening is recommended in first-degree family members of patients with SCAD in whom a monogenic vascular disease has been identified. ^[1]
• Routine clinical or genetic screening of asymptomatic relatives of patients with SCAD is not recommended.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Nate Michalak, B.A. Arzu Kalayci, M.D. [2]

Synonyms and keywords: SCAD

The natural history of spontaneous coronary artery dissection has not been well characterized. Early reports based on post-mortem examinations after sudden cardiac death suggest a dismal prognosis. However, recent studies demonstrate that the majority of patients survive initial hospitalization and have a favorable prognosis following clinical stabilization. Some of the complications of SCAD include extension of dissection, recurrence of dissection, myocardial stunning, myocardial infarction, congestive heart failure, cardiogenic shock, ventricular arrhythmia, and sudden cardiac death.

• The natural history of spontaneous coronary artery dissection (SCAD) has not been well characterized.
• Early reports based on post-mortem examinations and small case series suggest a dismal prognosis, with sudden cardiac death as the initial presentation in 28% of cases and an in-hospital mortality of 49%.^[1]
• In contrast, data from recent studies demonstrate that the majority of SCAD lesions heal spontaneously over time and achieve complete resolution on repeat angiography within one month among stabilized patients who survive initial hospitalization.^[2][3]
• The risk of recurrence has been reported in 10 to 30% of cases with a 3- to 10-year follow-up from different series that adopted a non-revascularization management approach.^{[2][4][5][6][7]}

Complications include:

• Extension of dissection
• Recurrence of dissection
• Myocardial stunning
• Myocardial infarction
• Congestive heart failure
• Cardiogenic shock
• Ventricular arrhythmia
• Sudden cardiac death
• Iatrogenic catheter-induced coronary artery dissection (prevalence of 3.4%, compared with <0.2% for standard coronary angiography)^[8][9]

• Long-term survival after an index SCAD episode appears to be better compared with that of acute coronary syndrome (ACS).
• The rate of major adverse cardiac events (MACE) is comparable between post-SCAD and post-ACS settings.
• The rates of in-hospital myocardial infarction and long-term MACE were 4.5% and 20%, respectively.^[10]
• Unsuccessful percutaneous coronary intervention (PCI) was observed in approximately one-third of cases.^[11]
• In-hospital prognosis was better in the conservative treatment group when compared with patients managed with PCI.^[10][12]
• A large cohort with a median follow-up of 3.1 years reported a post-discharge MACE rate of 19.9% (approximately 6 events/100 person-years), with myocardial infarction (16.8%) and recurrent SCAD (10.4%) as the most frequent events.^[7]