Aortic Dissection

EXECUTIVE SUMMARY

• Classic findings of aortic dissection are uncommon.
• Consider dissection when there is sudden onset of chest pain associated with visceral symptoms.
• Intravenous contrast-enhanced CT is the imaging modality that is often readily available and highly accurate.
• Intravenous beta-blockers should be the initial therapy in patients with the goal heart rate of around 60 beats per minute and systolic blood pressure of less than 120 mmHg.

Introduction

Aortic dissection is the result of a tear of the aortic intima that leads to bleeding within the aortic media and the development of a hematoma in this potential space. Blood spreads along the length of the aorta and may disrupt function of the aortic valve and compress the blood vessels along its course. The hematoma also may rupture into other spaces within the chest, including the pericardium, the pleura, or the mediastinum. Complications of aortic dissection result from blood loss and lack of oxygen-carrying capacity to tissues, mass effect from blood in the pericardium, and frank exsanguination. Essentially this means that with rupture of the aorta, death can occur within minutes as a consequence of blood loss or pericardial tamponade.

The first case of aortic dissection described in the medical literature was discovered in 1760 upon the death of King George II, who perished suddenly while straining on a toilet.¹ Like some other “classic” conditions, aortic dissection is relative rare; the incidence of acute myocardial infarction is estimated to be up to 1,000 times greater than aortic dissection.² Nonetheless, because aortic dissection is associated with high morbidity and rapid mortality, it is an important diagnosis to consider when evaluating patients with chest and back pain in the emergency department (ED).

Classification of Aortic Dissection

Aortic dissection is described in terms of location and acuity. This is important because the type and extent of the disease determines the need for surgical intervention. The two most commonly used classification systems for aortic dissection are Stanford and Debakey. In the Stanford system, dissections are delineated as Type A or B, and in the Debakey system, they are categorized as Types, I, II, or III.

Type A dissections are all those that involve any part of the aorta proximal to the brachiocephalic artery, and Type B dissections involve only the portion distal to the brachiocephalic artery. (See Figure 1.) Type I dissections are those that begin in the ascending aorta and extend to or beyond the arch. Type II are those dissections only in the ascending aorta, and Type III are only in the descending aorta. “Acute” aortic dissections are those found within two weeks of the onset of pain, while subacute are within two to six weeks. Dissections are considered “chronic” if they are found six weeks or more after the onset of pain.

Figure 1. Aortic Dissection Type A and Type B

Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography
© 2011-2016. All Rights Reserved.

Epidemiology

For several reasons, the incidence of aortic dissection can only be estimated. Many cases of sudden death may be attributable to aortic dissection, but since most of these are in the elderly, and relatively few autopsies are performed in older people, the deaths may be signed off as caused by a myocardial infarction or arrhythmia. Incidence of aortic dissection has been estimated between 2.5/100,000 and 6/100,000.^3,4 In comparison, the rate of aortic aneurysm rupture is double that. However, if limited only to patients who present to an ED complaining of back or chest pain, the rate of aortic dissection is reported to be as high as three out of 1,000.⁵ The International Registry of Acute Aortic Dissection (IRAD) published its first results in 2000. In that study, the mean age at onset was 63 years, and two out of three patients were male. Overall mortality was 27%, but this varied significantly depending on the type of dissection and whether surgical or medical management was undertaken. The mortality of untreated Type A aortic dissection increases 1-2% every hour following onset, and in-hospital mortality is between 15-30%.⁶ With successful initial therapy, the five-year survival rate of Type A dissections is 75%.

Women present with aortic dissection at a rate half that of men, but women are more likely to have atypical symptoms and a delayed diagnosis. For example, women are more likely than men to present with congestive heart failure or altered mental status.^7,8 As a result, women have a higher mortality rate.

Etiology and Pathophysiology

The aorta is a large, elastic artery composed of three layers: (see Figure 2)

• Intima: the inner layer covered in a single layer of endothelium;

• Media: the thickest layer composed of elastic tissue, smooth muscle cells, and collagen;

• Adventitia: the outer layer composed of loose connective tissue, which contains the vasa vasorum (the blood supply to the aortic wall).

Figure 2. Cross Section of Aorta

Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography
© 2011-2016. All Rights Reserved.

Aortic dissection is the result of a tear between the aortic intima and the inner layer of aortic media that allows blood to enter and split the layers of the aortic media. This leads to blood accumulation in the potential space called a false lumen. Pulsatile blood tears through the length of the aorta and disrupts flow in the true lumen, resulting in hypoperfusion of critical organs including brain, spine, gut, heart, and kidneys. Blood also may accumulate freely within the pericardium, stifling cardiac output. Free aortic wall rupture into the pleural space may result in blood loss and hypotension, along with respiratory compromise. This injury to the aortic wall can occur as a result of multiple factors: abnormal aortic wall stress, structural irregularities of the aortic media, or injury to the aortic wall.

Cystic medial necrosis, or cell death of the smooth muscle cells of the media, is described as a “prerequisite” for aortic dissection.⁹ Connective tissue disease, such as Marfan syndrome as well as chronic hypertension are both associated with this cell death process that weakens the aortic structure and predisposes patients with these conditions to aortic dissection. Aortic dissection also can occur via spontaneous hemorrhage of the vasa vasorum due to hypertension. This results in an intramural hematoma within the wall of the aorta and weakening of the media. Intramural hematomas are associated most commonly with Type B dissections in elderly patients.¹⁰

Genetic disorders are associated with aortic dissection. Marfan syndrome, Ehlers-Danlos syndrome, and aortoannular ectasia are all associated with increased risk of aortic dissection due to weakness of the aortic wall. Marfan syndrome is present in 50% of those presenting with aortic dissection who are younger than 40 years of age, and most patients with Marfan syndrome who present with dissection also have a family member who suffered a dissection.¹¹ Collagen vascular disease affects the mechanical properties of the aortic wall and the flow of blood through the aortic lumen, which contributes to weakness in the aortic wall and increased risk of dissection. Patients with bicuspid aortic valves also have a 5-18 times greater risk of aortic dissection compared to the general population, due to abnormal wall stress and presence of less elastic tissue in the aortic wall.^12,13

Hypertension is considered one of the most significant risk factors for aortic dissection. About 70-90% of patients with aortic dissection also have a diagnosis of hypertension. Smoking is not as strong a risk factor, but there are higher rates of tobacco abuse in patients diagnosed with aortic dissection.¹⁴ Stimulant use (i.e., cocaine, methamphetamine) and pheochromocytoma increase heart rate and stroke volume, which also can damage the aortic wall.

Chest pain is a common complaint among ED patients who use cocaine. In a recent case-control study of patients receiving ED care, 7% of patients with chest pain had a positive toxicology test for cocaine compared with 4% of controls (P < 0.001).¹⁵ Depending on the population studied, cocaine use was implicated in the diagnosis of aortic dissection anywhere from 0.5-37% of the time.^16,17 A more recent assessment of the IRAD database demonstrated a link between a history of cocaine use and aortic dissection 1.8% of the time. Cocaine users with aortic dissection tended to be younger, have a higher body mass index, and were more likely to smoke than other aortic dissection patients. The mortality rate in cocaine users was lower than for those with Type A dissection and no history of cocaine use, likely due to their younger age of presentation. History of hypertension, rates of atherosclerosis, and time from symptom onset to presentation were the same between cocaine users and those without a cocaine use history.¹⁸

Half of dissections that occur in women younger than 40 years of age are associated with pregnancy. Genetic abnormalities of the aortic valve or aortic wall are present in the majority of these cases, but the presentation can be spontaneous. Hormonal changes, coupled with increased heart rate and stroke volume as a result of the normal physiological changes of pregnancy, are associated with the increased risk of aortic dissection. Aortic dissection is diagnosed most commonly during the third trimester or early postpartum timeframe and should be considered in the differential diagnosis of chest pain in these patients.¹⁹

Clinical Features

Aortic dissection is a difficult diagnosis to make since it mimics so many more common diagnoses and often does not present with “typical” symptoms. Among the most worrisome historical concerns are:

• Acute, sudden-onset, severe chest pain;
• Family history of aortic disease;
• Known aortic valve disease, thoracic aortic aneurysm, or connective tissue disease;
• Recent aortic manipulation;
• Pain that is “ripping” or “tearing” in nature, or that migrates to the back or abdomen;
• Visceral symptoms of nausea, vomiting, sweating, apprehension, or lightheadedness.

About 4% of cases may be painless, especially in those patients with diabetes, prior diagnosis of aortic disease, or dissection of iatrogenic origin, and in older patients. There is increased mortality in these patients, often related to delay in diagnosis.²⁰

Physical exam findings described as “typical” in textbooks often are not present in patients with aortic dissection, and their absence cannot be relied upon to adequately exclude a patient with a high pretest probability of aortic dissection. Systolic blood pressure difference of > 20 mmHg previously has been reported as convincing evidence for aortic dissection,²¹ but new evidence suggests that up to 20% of unaffected people may have this finding.¹⁰ Similarly, a 2002 meta-analysis demonstrated that only 31% of patients with aortic dissection had pulse deficits or blood pressure differentials, and although the presence of these findings increased the possibility of aortic dissection, absence of the finding did not adequately exclude aortic dissection.²²

High-risk physical findings include:

• Pulse deficits or systolic blood pressure differential: both associated with worse outcomes;

• New-onset aortic regurgitation (especially if complicated by pericardial tamponade): new diastolic murmur, jugular venous distention, tachycardia and muffled heart sounds, hypotension;

• Syncope: present 13% of the time in aortic dissection, resulting from acute cardiac dysfunction or vascular outflow obstruction; associated with increased rates of stroke or other neurologic deficits and higher rates of death in the hospital;²³

• Hypotension or shock state: associated with worse outcomes, especially if related to aortic rupture or pericardial tamponade, the most common causes of death in Type A dissections;

• Focal neurologic deficits: stroke symptoms plus chest pain should raise a high level of concern for aortic dissection. Proximal arch dissections may cause intracranial deficits, while distal arch dissections can cause spinal cord and lower extremity weakness. It is critical to identify the presence of aortic dissection during stroke, as thrombolytic medications are contraindicated in this circumstance and can result in death.

• Mesenteric ischemia is the most common gastrointestinal complication of aortic dissection and also the most frequent cause of death in Type B dissection.⁸

Seemingly benign presentations, such as sore throat, hoarseness, or dysphagia, can be associated with mass effect from compression of the proximal aorta and aortic arch. (See Table 2.)

Diagnosis

Routine screening tests available to evaluate patients with chest pain in the ED are usually of limited utility in the diagnosis of aortic dissection. The primary value is to confirm the presence of another disease process, although aortic dissection can coexist with many other etiologies of chest, back, or abdominal pain. Electrocardiography, serum lab markers, and chest radiography are tests that can be obtained rapidly and usually routinely. CT angiography is the most useful imaging test to detect aortic dissection in the ED, but transesophageal echo also has some utility in the management of unstable patients.

Electrocardiography

The IRAD investigators found that the electrocardiogram (ECG) was normal in about 30% of cases. Another 2016 study retrospectively analyzed ECGs from patients with acute Type A aortic dissections and found that 38% of the time, acute ischemic changes were present, with 16% of patients having a concurrent ST-elevation myocardial infarction (STEMI). This may cause some clinicians concern since the treatment for a STEMI is significantly different than the treatment of aortic dissection. The 2010 American Heart Association (AHA) guidelines, however, state that patients with a low-risk history and physical exam for aortic dissection who present with ECG changes consistent with an acute coronary syndrome should be managed with coronary reperfusion therapy. Further imaging of the aorta should be undertaken only if no culprit lesion is detected on angiography.

Chest Radiography

Chest radiography is neither specific nor sensitive for aortic dissection, and is of limited value to make a diagnosis in most patients. A completely normal chest radiograph reduces the probability of aortic dissection in low-risk patients, and is a recommended study in low- and intermediate-risk patients. Contrast-enhanced CT of the chest is the diagnostic test of choice in those at high risk. A normal chest X-ray should not be used to rule out the disease in high-risk patients. A widened mediastinum or abnormal aortic contour increases the likelihood of aortic dissection, but was found to have a sensitivity of 64% in one prospective study.²⁴

Laboratory Analysis

Use of the D-dimer as a screening test to exclude aortic dissection in low-risk patients has not been evaluated in a large prospective trial. The AHA guidelines recommend against the use of D-dimer as a diagnostic tool in patients being evaluated for aortic dissection because of a lack of evidence supporting its use.⁸ The American College of Emergency Physicians (ACEP) guidelines state that although there are limitations to use of the D-dimer, using the lab test potentially may reduce unnecessary radiation exposure to some patients. Nonetheless, the ACEP guidelines also counsel “do not rely on D-dimer alone to exclude the diagnosis of aortic dissection.”²⁵

Computed Tomography

Newer multidetector CT (MDCT) scanners with 64 or more detector rows have nearly perfect specificity and sensitivity and are the recommended advanced imaging test for high-risk patients. They are available at most institutions and provide relatively rapid results. MDCT has the advantage over the other imaging modalities with the ability to image and reconstruct the entire aorta in three dimensions.²⁶ Evaluation for aortic dissection should be performed with triphasic CT angiography of the aorta (CTAA), which consists of unenhanced, arterial, and venous images. The initial noncontrast images should image from the lung apex to the upper abdomen. The arterial scans are obtained by administering a bolus-tracked set of images from lung apices to the groin. The delayed images (1-2 minutes later) assess for late filling of a false lumen, detect abdominal organ malperfusion, and contrast extravasation from a ruptured aorta. Electrocardiographic gating reduces overdiagnosis of aortic dissection due to motion artifact, and is becoming the standard of care. It also better detects the presence of complications of the proximal ascending aorta and aortic root, as well as the aortic valve and sinus.²⁷

The major risks of CTAA are IV contrast reactions, potential for decompensation outside the ED, and ionizing radiation exposure. CT may be relatively contraindicated in patients with impaired renal function. Non-contrast ECG-gated 128-slice CTAA may be the trend of the future, as the images obtained are high quality, associated with a lower dose of radiation, and have no risk of contrast reaction.²⁸

Figure 3. Contrast-enhanced CT of Type A Dissection at Aortic Root

Image courtesy of Paul Schoenhagen, MD, Imaging Institute, Cardiovascular Imaging, Cleveland Clinic

Figure 4. Intramural Hematoma Ascending Aorta

Image courtesy of Paul Schoenhagen, MD, Imaging Institute, Cardiovascular Imaging, Cleveland Clinic

Figure 5. Type A Dissection at Mid-ascending Aorta

Image courtesy of Paul Schoenhagen, MD, Imaging Institute, Cardiovascular Imaging, Cleveland Clinic

Figure 6. Type A Dissection with Multiplanar Reconstruction at Mid-ascending Level

Image courtesy of Paul Schoenhagen, MD, Imaging Institute, Cardiovascular Imaging, Cleveland Clinic

Ultrasound

Transesophageal echocardiography (TEE) not only eliminates the risk associated with radiation exposure and contrast reactions, but it can be performed at the patient’s bedside. According to a 2006 meta-analysis, TEE has a sensitivity of 98% and specificity of 95%.²⁹ The main issues with use of TEE are lack of universal availability, the need for conscious sedation (and the potential risks that ensue), and the speed with which images can be collected and analyzed since aortic dissection is a time-sensitive diagnosis.

Unfortunately, transthoracic echocardiography currently lacks the specificity and sensitivity of other imaging modalities and, therefore, is not recommended to definitively establish the diagnosis of aortic dissection per the ACEP guidelines.

Magnetic Resonance Imaging

The use of MRI is just as effective at determining the presence of aortic dissection as CT and TEE, but it is used only about 1% of the time for acute diagnosis. Monitoring a potentially unstable patient during a long MRI examination is difficult, but with newer technology, faster scanning times may be realized. MRI may be appropriate for pregnant patients and those with renal disease or IV contrast allergy.

Differential Diagnosis

The list of possible alternative diagnoses is incredibly broad, and includes most conditions that cause chest, back, or abdominal pain. (See Table 3.)

ED Management and Disposition

Management strategies differ depending on the location of the dissection. In general, Type A dissections are managed surgically, while Type B dissections are more amenable to medical management. The primary goals of ED treatment should be stabilization and pain control, along with expedited consultation by a thoracic surgeon and intensive care unit team. Many hospitals do not have the resources to manage the complex care needs of a patient with aortic dissection appropriately, so priority should be given to early detection and coordination of care with a regional center of excellence.³⁰ Initial ED resuscitation is very similar for both Type A and Type B dissections.

Shock occurs in up to 20% of patients with aortic dissection and is associated with increased mortality and more frequent complications. Patients with shock are more likely to have comorbidities of hypertension, diabetes, and atherosclerosis. They are more likely to have evidence of “typical” aortic dissection features, such as migratory chest pain, pulse deficits, or neurological deficits. Radiologic findings of a widened mediastinum and pericardial effusions also are detected more frequently in patients with shock. Although patients with aortic dissection and shock have higher in-hospital mortality, if they survive to discharge from the hospital, their five-year mortality is similar to those who did not have shock.³¹

Shock is often the result of pericardial tamponade in this setting. Some evidence suggests that pericardiocentesis should be delayed in patients with a pulse, with priority given to expedited transfer to the OR.³² Historically, pericardiocentesis was thought to result in propagation of the dissection or worsened leak due to increased arterial pressure. A more recent, small case series showed that controlled pericardiocentesis could be lifesaving in the setting of critical pericardial tamponade without immediately available thoracic surgery.³³ The authors concluded that when thoracic surgery is not readily available, small volume pericardiocentesis (repeated aspiration of 5-10 mL) can be performed without an increased risk of death or decompensation. The 2010 AHA guidelines recommend that just enough fluid be removed to restore perfusion.⁸

Other potential causes of shock associated with aortic dissection are:

• Aortic rupture;
• Aortic insufficiency and heart failure;
• Myocardial infarction;
• Pseudohypotension, which especially should be considered if patient appears well. (See Table 4.)

Falsely decreased blood pressure can occur when a proximal dissection involves the brachiocephalic artery. It is important to check blood pressure in both arms.

In most cases, treatment of shock associated with aortic dissection should be managed with rapid surgical intervention, but this may not be readily available in many hospital and free-standing EDs. At sites without immediate availability of thoracic surgery, attempts must be made to stabilize the patient prior to transport. The need for intubation should be considered. Volume expansion with crystalloid is a first-line intervention for resuscitation, and vasopressors may be required for refractory hypotension.³⁴ Nonoperative treatment options for shock related to aortic dissection are limited, and little evidence is available to support many of the interventions. Vasopressors can be used to support perfusion, but their use may result in further propagation of the false lumen.⁸ Norepinephrine and phenylephrine are the preferred pressors. The goal of treatment of shock should be titration to a mean arterial pressure of 70 mmHg.³⁵

In patients without shock, reducing blood pressure and heart rate decreases stress on the compromised aortic wall. Chronotropic medications and vasodilators are used to achieve goal heart rate of 60 beats per minute and systolic blood pressure less than 120 mmHg, although there are limited data to support specific targets. The ACEP guidelines emphasize that although reducing heart rate and blood pressure may reduce the risk of further dissection, extremely aggressive attempts at doing so may result in adverse outcomes in patients with aortic insufficiency and pericardial tamponade — both conditions that are preload-dependent.²⁵

Large trials have demonstrated improved survival in patients with aortic dissections managed with beta blockers and calcium channel blockers. The AHA guidelines recommend beta blockers as a first-line treatment, with calcium channel blockers or angiotensin-converting enzyme (ACE) inhibitors as acceptable alternatives in patients with contraindications to beta blockade. Use of calcium channel blockers may convey a survival benefit in patients with Type B dissections.³⁶ Intravenous opiates should be administered to control pain. Vasodilators should be given if systolic blood pressure > 120 mmHg after beta blockade and pain control. Intravenous nitroprusside is a commonly used agent. Often, patients have refractory hypertension and require multiple agents to achieve an optimal blood pressure. Caution should be given to initiate vasodilators only after administering appropriate rate control medications due to the risk of reflex tachycardia and worsened stress on the arterial wall.

Surgery is indicated in patients with Type A dissection, as mortality is extremely high for medically managed patients. The long-term survival rates for those with successful surgery who survive to hospital discharge are more than 90% in experienced centers. The risk of death depends on the patient’s age and the patient’s post-event stability, including presence of shock, tamponade, congestive heart failure, coma, stroke, renal failure, or mesenteric ischemia. Unstable and chronically ill patients have a 31% rate of perioperative death compared to 17% of patients without those risks. Endovascular stent grafts are not indicated for repair of the ascending aorta or aortic arch. Surgical management in most patients with Type A dissection involves removal of the aortic root and replacement with a tube graft. If the aortic valve is structurally sound, it is not replaced. Extensive dissections involving the aortic arch are technically challenging to treat and generally are managed only in aortic centers of excellence. For patients with severe comorbid disease or who are moribund, comfort care may be offered as an alternative to surgical treatment.

Medical management usually is recommended for Type B dissections unless there is propagation of the dissection, compromise of major branches of the aorta, shock, periaortic hematoma, mesenteric ischemia, spinal cord or limb ischemia, renal failure, persistent pain despite treatment, or bleeding into the pleural cavity. Invasive treatment for Type B dissections includes both surgery and endovascular treatment. Invasive treatments are more likely to be offered to patients younger than 70 years of age. Patients with complicated Type B dissections generally have a poor prognosis, and invasive management is recommended in these patients. The in-hospital mortality rate of complicated Type B aortic dissection is around 20%, and is significantly higher in patients older than 70 years of age.³⁷

Medicolegal Issues and Missed Diagnoses

With regard to medicolegal considerations, aortic dissection exists at the intersection of rare and lethal. Even the AHA guidelines set realistic expectations, stating that in patients without a high-risk history or physical exam, delays in care and increased mortality are likely.⁸ Within the last decade, the saga of the delayed diagnosis of aortic dissection in a celebrity and the resulting multimillion dollar lawsuit has been played out in the national media.³⁸ An analysis of litigated cases and formal complaints published by the Canadian Medical Protective Association, although small in number of included patients, identified multiple pitfalls of aortic dissection diagnosis. In this series, only 22% of missed cases were in patients with classic risk factors such as Marfan syndrome. Although more than 90% presented with severe chest pain, only 3% described it as “tearing” in nature. In 11 cases in which upper extremity blood pressures were documented, only one case demonstrated an abnormality. Of the 18 cases in which pulses were documented, only two patients had a pulse deficit detected. Among the most common incorrect diagnoses were:

• Acute coronary syndrome (19%);
• Musculoskeletal disorder (20%);
• Pneumonia or pulmonary embolism (20%);
• Pericarditis (12%);
• Gastritis/esophageal spasm (9%);
• Other: common cold, renal colic, pharyngitis, thyroiditis (20%).

The authors concluded that aortic dissection should be considered in patients with sudden onset of chest pain, accompanying visceral symptoms (such as diaphoresis, pallor, and nausea), or a normal or minimally abnormal ECG. Over-reliance on absence of “classic” features, such as tearing or migratory pain, pulse deficits, or a widened mediastinum on chest radiography, can lead to a missed diagnosis. However, in patients with a low likelihood of aortic dissection, absence of classic aortic dissection history, physical, or workup findings should be documented, along with a medical decision-making note stating consideration of the disease process and rationale for not pursuing definitive imaging.³⁹

REFERENCES

1. Criado J. On the death of King George II in 1760: Aortic dissection in perspective. Available at: http://www.vasculardiseasemanagement.com/content/on-death-king-george-ii-1760-aortic-dissection-perspective. Accessed Aug. 8, 2016.
2. Tsai TT, Trimarchi S, Nienaber CA. Acute aortic dissection: Perspectives from the International Registry of Acute Aortic Dissection (IRAD). Eur J Vasc Endovasc Surg 2009;37:149-159.
3. Melvinsdottir IH, Lund SH, Agnarsson BA, et al. The incidence and mortality of acute thoracic aortic dissection: Results from a whole nation study. Eur J Cardiothorac Surg 2016; pii: ezw235. [Epub ahead of print].
4. Howard DP, Banerjee A, Fairhead JF, et al; Oxford Vascular Study. Population-based study of incidence and outcome of acute aortic dissection and premorbid risk factor control: 10-year results from the Oxford vascular study. Circulation 2013;127:2031-2037.
5. Tsai TT, Trimarchi S, Nienaber CA. Acute aortic dissection: Perspectives from the International Registry of Acute Aortic Dissection. Eur J Vascr Endovasc Surg 2009;37:149-159.
6. Trimarchi S, Eagle KA, Nienaber CA, et al. Role of age in acute type A aortic dissection outcome: Report from the International Registry of Acute Aortic Dissection (IRAD). J Thorac Cardiovasc Surg 2010;140:784-789.
7. Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection (IRAD): New insights into an old disease. JAMA 2000;283:897-903.
8. Hiratzaka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. Circulation 2010;121:e266-369.
9. Kamalakannan D, Rosman HS, Eagle KA. Acute aortic dissection. Crit Care Clin 2007;23:779-800.
10. Upadhye S, Schiff K. Acute aortic dissection in the emergency department: Diagnostic challenges and evidence-based management. Emerg Med Clin North Am 2012;30:307-327.
11. Weinsaft JW, Devereux RB, Preiss LR, et al. Aortic dissection in patients with genetically mediated aneurysms: Incidence and predictors in the GenTAC registry. J Am Coll Cardiol 2016;67:2744-2754.
12. Januzzi JL, Isselbacher EM, Fattori R, et al; International Registry of Aortic Dissection (IRAD). Characterizing the young patient with aortic dissection: Results from the International Registry of Aortic Dissection (IRAD). J Am Coll Cardiol 2004;43:665-669.
13. Parai JL, Masters RG, Walley VM, et al. Aortic medial changes associated with bicuspid aortic valve: Myth or reality? Can J Cardiol 1999;15:1233-1238.
14. Melvinsdottir IH, Lund SH, Agnarsson BA, et al. The incidence and mortality of acute thoracic aortic dissection: Results from a whole nation study. Eur J Cardiothorac Surg 2016 Jun 22 [epub ahead of print].
15. Maric T, O’Connor S, Pollock N, et al. Prevalence of cocaine use among patients attending the emergency department with chest pain. Emerg Med J 2010;27:548-550.
16. Eagle K, Isselbacher EM, DeSanctis RW; International Registry for Aortic Dissection (IRAD) Investigators. Cocaine-related aortic dissection in perspective. Circulation 2002;105:1529-1530.
17. Hsue PY, Salinas CL, Bolger AF, et al. Acute aortic dissection related to crack cocaine. Circulation 2002;105:1592-1595.
18. Dean JH, Woznicki EM, O’Gara P, et al. Cocaine-related aortic dissection: Lessons from the International Registry of Aortic Dissection. Am J Med 2014;127:878-885.
19. Yuan SM. Aortic dissection during pregnancy: A difficult clinical scenario. Clin Cardiol 2013;36:576-584.
20. Tolenaar JL, Hutchison SJ, Montgomery D, et al. Painless type B aortic dissection: Insights from the International Registry of Acute Aortic Dissection. Aorta 2013;1:96-101.
21. von Koloditsch Y, Schwartz AG, Nienaber CA. Clinical prediction of acute aortic dissection. Arch Intern Med 2000;160:2977-2982.
22. Klompas M. Does this patient have an acute thoracic aortic dissection? JAMA 2002;287:2262-2272.
23. Nallamothu BK, Mehta RH, Saint S, et al. Syncope in acute aortic dissection: Diagnostic, prognostic, and clinical implications. Am J Med 2002;113:468-471.
24. von Kodolitsch Y, Nienaber CA, Dieckmann C, et al. Chest radiography for the diagnosis of acute aortic syndrome. Am J Med 2004;116:73–77.
25. Diercks DB, Promes SB, Schuur JD, et al. Clinical policy: Critical issues in the evaluation and management of adult patients with suspected acute nontraumatic aortic dissection. Ann Emerg Med 2015;65:32-42.
26. Baliga RR, Nienaber CA, Bossone E, et al. The role of imaging in aortic dissection and related syndromes. JACC Cardiovasc Imaging 2014;7:406-424.
27. Valente T, Rossi G, Lassandro F, et al. MDCT evaluation of acute aortic syndrome (AAS). Br J Radiol 2016;89:20150825.
28. Russo V, Garratoni M, Buia F, et al. 128-slice CT angiography of the aorta without ECG-gating: Efficacy of faster gantry rotation time and iterative reconstruction in terms of image quality and radiation dose. Eur Radiol 2016;26:359-369.
29. Shiga T, Wajima Z, Apfel CC, et al. Diagnostic accuracy of transesophageal echocardiography, helical computed tomography, and magnetic resonance imaging for suspected thoracic aortic dissection: Systematic review and meta-analysis. Arch Intern Med 2006;166:1350–1356.
30. Chavanon O, Baguet JP, Albaladejo P, et al. Direct admission to the operating room: An efficient strategy for patients diagnosed or highly suspected acute type A aortic dissection. Can J Cardiol 2011;27:685-691.
31. Bossone E, Pyeritz RE, Braverman AC, et al. Shock complicating type A acute aortic dissection: Clinical correlates, management, and outcomes. Am Heart J 2016;176:93-99.
32. Isselbacher EM, Cigarroa JE, Eagle KA. Cardiac tamponade complicating proximal aortic dissection. Is pericardiocentesis harmful? Circulation 1994;90:2375-2378.
33. Cruz I, Stuart B, Caldeira D, et al. Controlled pericardiocentesis in patients with cardiac tamponade complicating aortic dissection: Experience in a centre without cardiothoracic surgery. Eur Heart J Acute Cardiovasc Care 2015;4:124-128.
34. Strayer R, Shearer PL, Hermann LK. Screening, evaluation, and early management of acute aortic dissection in the ED. Curr Cardiol Rev 2012;8:152-157.
35. Isselbacher EM, Ianuzzi JL. Medical therapy and acute surveillance. In: Baliga R, Nienaber C, Isselbacher EM, Eagle KA. Aortic Dissection and Related Syndromes. New York: Springer Science & Business Media; 2007:145-152.
36. Suzuki T, Isselbacher EM, Nienaber CA, et al. Type-selective benefits of medications in treatment of acute aortic dissection (from the International Registry of Acute Aortic Dissection [IRAD]). Am J Cardiol 2012;109:122-127.
37. Jonker FHW, Trimarchi S, Muhs BE, et al; IRAD Investigators. The role of age in complicated acute type B aortic dissection. Ann Thorac Surg 2013;96:2129-2134.
38. Considine B. Jon Ritter’s widow talks about wrongful death suit. Available at: http://www.today.com/popculture/john-ritters-widow-talks-about-wrongful-death-suit-2D80555805. Accessed Aug. 26, 2016.
39. The Canadian Medical Protective Association. Aortic dissections: “Tearing” apart the data. Available at: https://www.cmpa-acpm.ca/-/aortic-dissections-tearing-apart-the-data. Accessed Aug. 27, 2016.