History

• Earlier medical history is significant; known aortic aneurysm, congenital heart disease, connective tissue disease, hypertension, and previous surgical or catheter-based cardiac procedure increases likelihood of acute aortic syndrome ^c1c2c3c4c5
• Seek history of stimulant drug use (eg, cocaine, methylenedioxymethamphetamine, methamphetamine) ^c6c7c8
• Symptom onset is sudden and rapid
• Clinical symptoms do not allow distinction between acute aortic syndrome types and other acute pathologic conditions.
• For all types of acute aortic syndrome, broad range of nonspecific symptoms are possible, depending on location of dissection, degree of extension, presence of vascular branch (and end-organ) involvement, and presence of rupture
  • Aortic dissection
    • Symptomatic in 80% to 90% of cases ^r4
    • Sudden-onset severe chest pain is first symptom ^c9
      • Most patients describe pain as sharp and knife-like; others describe it as tearing or ripping ^r3r8c10
      • Abruptness of onset is a specific characteristic (84%) ^r8
      • Location of pain may reflect site of origin of intimal tear
        • Typically anterior chest pain in type A (80% of cases), but 47% of patients also report back pain ^r3r9c11c12
        • Begins as back pain in type B (64% of cases), but presentation with chest and/or abdominal pain also occurs ^r3c13c14c15
        • Pain may be migratory as dissection extends ^c16
    • May present with syncope (15% with type A; less than 5% with type B) ^r7c17c18
    • Other symptoms reflect ischemic end-organ dysfunction caused by extension of dissection to branch arteries
      • Diffuse abdominal pain is present in about 21% of type A cases and about 43% of type B cases ^r3c19c20
      • Flank pain and decreased urine output are likely if renal artery is involved in dissection ^c21c22
      • Dyspnea and orthopnea are likely if ischemic congestive heart failure is present or if left ventricular failure results from aortic rupture into left atrium ^c23c24c25c26
      • Symptoms of stroke are likely if carotid artery is involved
      • Lower extremity numbness and pain are likely if dissection extends to iliac arteries (with paraplegia if spinal arteries are not perfused) ^c27c28c29
      • Rarely, hemoptysis is caused by rupture into tracheobronchial tree ^c30
      • Rarely, hematemesis is caused by rupture into esophagus ^c31
  • Intramural hematoma
    • Patient is more likely to be older and more likely to be female than in aortic dissection ^r4
    • Presents with pain similar to that of aortic dissection ^r4c32c33
    • Less likely to present with neurologic symptoms
  • Penetrating atherosclerotic ulcer ^r10
    • Patient is more likely to be an older man and more likely to have known coronary artery disease or risk factors for atherosclerotic disease, than in aortic dissection ^r7c34c35
    • Presents with pain similar to that of aortic dissection ^r3r4c36c37
    • Rarely presents with symptoms of dissection-related lack of organ perfusion

Physical examination

• May appear anxious and diaphoretic ^c38c39
• Blood pressure may be high, normal, or low ^r11
  • Measure blood pressure in both arms; highest reading will be used to determine blood pressure management plan ^r3
  • Type A dissection
    • Hypotension in about 25% ^r8c40
    • Hypertension in about 35% ^r8c41
  • Type B dissection
    • Hypertension in about 70% ^r8c42
• Cardiopulmonary examination
  • Pulse deficit (apical versus radial) is present in about 18% of type A cases and about 9% of type B cases ^r8c43c44
  • Pressure differential (interarm blood pressure difference) greater than 20 mm Hg is suggestive (although studies differ on its significance) ^r9c45
    • Compare carotid and femoral arteries
  • Aortic insufficiency murmur (early diastolic decrescendo murmur heard best in the left third intercostal space) is present in about 44% of type A cases and about 12% of type B cases ^r8c46c47
  • Signs of congestive heart failure (eg, rales, S₃ gallop) are present in about 9% of type A cases and about 3% of type B cases ^{r8c48c49c50c51}
  • Cool, pale lower extremities with decreased or absent pulses are likely if iliac and femoral arteries are involved ^{c52c53c54c55c56c57c58c59}
• Neurologic examination
  • Signs of stroke are present in about 6% of type A cases and about 2% of type B cases ^r8
  • Hemiparesis is likely if spinal artery malperfusion is present ^c60
  • Hoarseness (from laryngeal nerve compression) may occur ^c61

Causes

• Often multifactorial; most common factors include uncontrolled hypertension and inherited susceptibility ^r5
  • Hypertension ^c62
    • Elevated systolic pressure can propagate an aortic dissection ^c63
    • Physical exertion or emotional stress is direct precursor of pain in two-thirds of aortic dissection events; both involve acute changes in blood pressure ^r11c64c65
  • Genetic syndromes ^c66
    • Congenital connective tissue diseases (associated with abnormalities of aortic media) ^c67
      • Marfan syndrome ^r12c68
        • Autosomal dominant genetic disorder characterized by weakness of connective tissues (which endangers heart and blood vessels)
        • Aortic dissection occurs in 15% to 50% of patients with Marfan syndrome who are younger than 40 years ^r11
      • Ehlers-Danlos syndrome type IV ^r13c69
        • Autosomal dominant genetic disorder characterized by skin hyperextensibility, joint hypermobility, and tissue fragility (which endangers heart and blood vessels)
        • Arterial complications are the leading cause of death
      • Loeys-Dietz syndrome ^c70
        • Autosomal dominant genetic disorder characterized by arterial tortuosity, wide-set eyes, cleft palate, and aortic dissection and aneurysm
    • Other familial thoracic aneurysm and dissection syndromes ^c71
      • Familial Marfan-like habitus ^c72
      • Familial ectopia lentis ^c73
      • Familial aortic dissection ^c74
      • Erdheim cystic medial necrosis ^c75
      • Congenital contractural arachnodactyly ^c76
    • Turner syndrome ^c77
      • Phenotypic female with 45,X karyotype
      • May have associated bicuspid aortic valve and/or aortic coarctation

Risk factors and/or associations ^r14

Primary diagnostic tools

• History and physical examination findings suggest the diagnosis, but a high index of suspicion is necessary given overlap with more common conditions ^r5c109
  • Best predictors are:
    • Abruptness of chest pain
    • Tearing or ripping quality of pain with migration
    • History of hypertension
    • Pulse deficit
    • Focal neurologic deficits
  • Consider risk scoring to determine pretest probability of acute aortic syndrome to direct testing strategy ^r25
    • 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines^r3 recommend this strategy, but a 2015 clinical policy from the American College of Emergency Physicians^r9 recommends against using this score to direct testing
      • High-risk history includes known aortic aneurysm or aortic valve disease, connective tissue diseases (eg, Marfan syndrome), familial or genetic aortic aneurysm/dissection syndromes, and recent surgical manipulation of aorta (surgical or catheter-based)
      • High-risk pain features and physical signs include abrupt onset of severe sharp or ripping chest/back/abdominal pain, presence of pulse deficit, blood pressure differential of more than 20 mm Hg between limbs, new murmur of aortic insufficiency, or new focal neurologic deficit
      • Risk category: ^r3
        • 2 or more high-risk features: high risk
        • 1 high-risk feature: intermediate risk
        • 0 high-risk features: low risk
• Obtain imaging based on risk group ^r3r7
  • Obtain urgent definitive aortic imaging (without waiting for chest radiograph) for all high-risk patients; if first aortic image finding is negative, obtain second imaging study for all high-risk patients or when suspicion is otherwise high ^r3
    • CT angiography is diagnostic test of choice for most patients with high-risk features ^r3r26
    • Bedside transesophageal echocardiography can be used for patients with suspected type A disease when CT is not feasible owing to hemodynamic instability ^r3
      • Transthoracic echocardiography has poor sensitivity and cannot be considered definitive imaging
    • MRI is an additional option if immediately available ^r3
  • Order chest radiograph for all patients who are at low or intermediate risk, primarily to identify other causes of chest pain, which may obviate the need for definitive aortic imaging ^r3
    • If dilated aorta or widened mediastinum is seen, proceed to definitive aortic imaging; chest radiograph alone is not sufficiently sensitive or specific for diagnosis of acute aortic syndrome
    • For patients at intermediate risk, proceed to definitive aortic imaging after chest radiograph if no alternative cause of symptoms has been identified
    • For patients at low risk, consider definitive aortic imaging if clinical scenario is suggestive and no alternative explanation for symptoms has been identified
• Consider D-dimer testing, although do not use a specific result to direct further testing or treatment ^r27
  • European Society of Cardiology guidelines^r7 recommend obtaining D-dimer level; a negative result in a patient with pretest low-risk status decreases likelihood of aortic dissection ^r28
  • American College of Emergency Physicians guidelines^r9 and 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines^r3 do not recommend routine D-dimer testing
• Additional testing is not diagnostic for acute aortic syndrome, but it is directed at differential diagnosis, identification of complications, and expediting time to surgery (for high-risk patients)
  • ECG and troponin levels ^r3
  • European Society of Cardiology guidelines^r7 suggest the following be obtained routinely: CBC and levels of creatinine, AST, ALT, C-reactive protein, procalcitonin, lactate, and blood gases
  • Obtain presurgical laboratory testing for all high-risk patients, including CBC, coagulation tests, serum chemistry, and blood type and screen ^r3

Laboratory

• D-dimer level ^c110
  • Elevated D-dimer level, especially in the first hour, increases suspicion of aortic dissection, but it cannot be used as diagnostic biomarker ^r7r29
    • D-dimer level increases precipitously in aortic dissection compared with other disorders, in which the D-dimer level increases gradually ^r7
  • Low D-dimer level is associated with decreased probability, but more research is needed; not recommended as screening tool^r9r3
    • With a cutoff of 0.5 mcg/mL ^r25r27r29
    • Intramural hematoma and penetrating atherosclerotic aortic ulcer may still be present even with D-dimer levels below this cutoff ^r7

Imaging

• CT angiography ^r30c111
  • Diagnostic test of choice for most patients ^r30
    • Test sensitivity and specificity are both 100% ^r3
  • Requires hemodynamic stability sufficient for transport to radiology department
  • Quickly and reliably detects aortic dissection, intramural hemorrhage, and penetrating atherosclerotic ulcer and allows for interventional planning
  • Best images are obtained with arterial phase imaging, ECG gating,^r31 and inclusion of entire length of aorta plus iliac and femoral vessels
• Transesophageal echocardiography ^c112
  • Useful in ascending and descending thoracic aortic dissection ^r32
    • Often cannot clearly visualize the proximal aortic arch owing to tracheal interference ^r32
  • Able to determine presence of hemopericardium and presence/severity of aortic regurgitation
  • Mid and distal abdominal aorta and branch vessels are often poorly visualized ^r32
  • Performed under conscious sedation or general anesthesia
  • Can be performed at bedside in hemodynamically unstable patients who would not tolerate transport
• Magnetic resonance angiography ^r26c113
  • Sensitivity and specificity are similar to those of CT, but the procedure is more time-intensive
    • Use is not appropriate in urgent situations
  • Gadolinium contrast material is less nephrotoxic than the iodinated contrast material used in CT scanning
• Chest radiography ^r26c114c115
  • Order chest radiograph for all patients who are at low or intermediate risk, primarily to identify other causes of chest pain, which may obviate the need for definitive aortic imaging

Other diagnostic tools

• Can be used in addition to risk category scores
• Aortic Dissection Risk Score (ADD-RS)
  • 1 point for risk factor (Marfan syndrome, family history of aortic disease, recent aortic condition or procedure)
  • 1 point for pain feature
  • 1 point for clinical exam feature
  • ADD-RS alone or with D-dimer may be a useful screening test to determine whether to proceed with imaging
• AORTA score ^r25
  • 1 point each for thoracic aortic aneurysm, severe pain, sudden pain, pulse deficit, or neurologic deficit
  • 2 points for hypotension
  • AORTA score over 2 combined with elevated D-dimer may help guide imaging decisions

Most common ^r14

• Acute coronary syndrome ^c116d1
  • Chest pain is usually the primary symptom in both scenarios; it is more likely to be of very abrupt onset and described as knife-like or tearing with acute aortic syndrome
  • Pulse differential and interarm blood pressure differential are unlikely in myocardial infarction
  • ECG may not always be helpful. Dissection-related coronary artery malperfusion may present with ECG changes that are indistinguishable from those of primary myocardial ischemia ^r3
  • Differentiate with immediate definitive aortic imaging (usually CT angiography) if patient is at intermediate or high risk for acute aortic syndrome
  • Myocardial infarction can coexist with aortic dissection, often as a complication thereof
• Pulmonary embolism ^c117d2
  • May present with similar symptoms (eg, chest pain, dyspnea, syncope), although character of pain is more likely to be pleuritic with pulmonary embolism. Dyspnea may be a prominent symptom with pulmonary embolism
  • D-dimer level is elevated in both conditions; it typically rises faster (within first few hours) with aortic dissection, but it is not diagnostically helpful for differentiation
  • Differentiate with CT angiography
• Pneumothorax ^c118
  • Usually presents with dyspnea and sudden onset of ipsilateral chest pain described most commonly as pleuritic rather than tearing
  • Physical examination may suggest the diagnosis, with ipsilateral decreased breath sounds, absence of tactile fremitus, and hyperresonance to percussion; cyanosis, hypotension, and tracheal deviation are usually present in tension pneumothorax
  • Differentiate with posteroanterior chest radiograph, which shows loss of lung markings in periphery and a pleural line that runs parallel to chest wall
• Acute mesenteric ischemia ^c119d3
  • Usually presents with acute onset of severe periumbilical pain disproportionate to physical examination findings, as opposed to pain of acute aortic dissection, which begins in chest and back and involves radiation of pain as dissection progresses
  • Patients with both conditions often have known cardiovascular disease or risk factors for cardiovascular disease
  • May occur as isolated event (usually due to thrombosis or emboli) or may occur secondary to aortic dissection extending to branch arteries off of abdominal aorta
  • Differentiate the 2 conditions with CT angiography, imaging the complete abdominal aorta and abdominal branch arteries
• Perforated peptic ulcer ^c120d4
  • Presents with pain typically limited to abdomen in contrast to pain of acute aortic syndrome, which usually begins in chest and/or back
  • Patients with perforated peptic ulcer usually have rigid abdomen and remain motionless with pain; those with aortic dissection usually do not have rigid abdomen and often writhe in pain
  • Erect chest radiograph shows subdiaphragmatic air in perforated peptic ulcer
  • Differentiate acute aortic syndrome from perforated peptic ulcer with CT angiography if there is diagnostic uncertainty

Admission criteria

Recommendations for specialist referral ^r1

• Obtain immediate urgent consult with cardiovascular surgeon upon diagnosis of acute aortic syndrome

Drug therapy

• Blood pressure and heart rate management
  • β-blockers ^c121
    • Labetalol ^c122
      • Labetalol Hydrochloride Solution for injection; Children and Adolescents: 0.2 to 1 mg/kg IV bolus (Max: 40 mg), then 0.25 to 3 mg/kg/hour continuous IV infusion.
      • Labetalol Hydrochloride Solution for injection; Adults: 10 to 20 mg IV, then 20 to 80 mg IV every 10 to 30 minutes until goal blood pressure is attained. Max cumulative dose: 300 mg.
    • Esmolol ^c123
      • Esmolol Hydrochloride Solution for injection; Adults: 500 to 1,000 mcg/kg IV over 1 minute, then 50 mcg/kg/minute continuous IV infusion, initially. Repeat bolus and titrate by 50 mcg/kg/minute until goal blood pressure is attained. Max: 200 mcg/kg/minute.
    • Propranolol ^c124
      • Propranolol Hydrochloride Solution for injection; Neonates†: 0.01 mg/kg/dose IV push over 10 minutes, repeated every 6 to 8 hours as needed. Titrate gradually as needed; heart rate may be dose-limiting. Max: 0.15 mg/kg/dose.
        • Off-label use in this age group
      • Propranolol Hydrochloride Solution for injection; Children and Adolescents: 0.01 mg/kg/dose IV push over 10 minutes, repeat every 6 to 8 hours as needed. May titrate dosage gradually as needed. Max: 0.15 mg/kg/dose or 3 mg/dose.
      • Propranolol Hydrochloride Solution for injection; Adults: Limited data suggest continuous IV at a rate of 2 to 3 mg/hour may be effective in post-surgical patients who cannot tolerate oral therapy; infusions were given for up to 9 days.
    • Metoprolol ^r3c125
      • Metoprolol Tartrate Solution for injection; Adults: 2.5 to 5 mg IV bolus over 1 to 2 minutes; may repeat every 5 minutes to a maximum of 3 doses.
  • Calcium channel blockers ^c126
    • For β-blocker–intolerant patients, verapamil or diltiazem may be used to reduce heart rate or to reduce blood pressure without causing reflex tachycardia ^r42
    • Verapamil ^r3r42c127
      • Verapamil Hydrochloride Solution for injection; Children and Adolescents: Initially, 0.1 to 0.3 mg/kg (ie, 2 to 5 mg) IV bolus, given over at least 2 minutes. Max single dose: 5 mg. If no response, repeat dose in 30 minutes. Max total dose: 10 mg.
      • Verapamil Hydrochloride Solution for injection; Adults: Initially, 5 to 10 mg (0.075-0.15 mg/kg) IV over at least 2 minutes. If no adequate response after 30 minutes, may give an additional 10 mg (0.15 mg/kg). An optimal interval for subsequent doses has not been determined and should be individualized for each patient. Clinical practice guidelines recommend 2.5 to 5 mg IV over 2 minutes. If no therapeutic response or adverse reaction is seen, may administer repeated doses of 5 to 10 mg every 15 to 30 minutes up to a total dose of 20 mg. Alternative dosing is 5 mg IV every 15 minutes, up to a total dose of 30 mg.
    • Diltiazem ^r3r42c128
      • Diltiazem Hydrochloride Solution for injection; Infants older than 7 months†, Children†, and Adolescents†: 0.25 mg/kg IV over 5 minutes followed by 0.05 to 0.15 mg/kg/hour continuous IV infusion (mean 0.11 mg/kg/hour) has been reported.
      • Diltiazem Hydrochloride Solution for injection; Adults: Initially, 0.25 mg/kg IV bolus over 2 minutes. After 15 minutes, 0.35 mg/kg over 2 minutes may be given. Individualize as needed. A 10 mg/hour IV infusion is started immediately after IV bolus. Some patients respond to lower doses (eg, 5 mg/hour). Max: 15 mg/hour.
    • Nicardipine (indicated as vasodilator for hypertension) ^c129
      • Nicardipine Hydrochloride Solution for injection; Neonates: 0.5 to 1 mcg/kg/minute continuous IV infusion, initially. Titrate every 15 to 30 minutes until goal blood pressure is attained. Usual dose: 0.5 to 2 mcg/kg/minute. Max: 6 mcg/kg/minute.
      • Nicardipine Hydrochloride Solution for injection; Infants, Children, and Adolescents: 30 mcg/kg (Max: 2 mg) IV, then 0.5 to 4 mcg/kg/minute continuous IV infusion, initially. Titrate by 1 mcg/kg/minute every 15 to 30 minutes until goal blood pressure is attained. Max: 10 mcg/kg/minute.
      • Nicardipine Hydrochloride Solution for injection; Adults: 5 mg/hour continuous IV infusion, initially. Titrate by 2.5 mg/hour every 5 to 15 minutes until goal blood pressure is attained. Max: 15 mg/hour.
  • Sodium nitroprusside ^c130
    • Used in conjunction with β-blocker to offset tachycardia caused by nitroprusside
      • Sodium Nitroprusside Solution for injection; Infants, Children, and Adolescents: 0.3 to 3 mcg/kg/minute continuous IV infusion, initially. Titrate every 5 minutes until desired effect or blood pressure cannot be further reduced without compromising organ perfusion. Max: 10 mcg/kg/minute for 10 minutes.
      • Sodium Nitroprusside Solution for injection; Adults: 0.3 to 0.5 mcg/kg/minute continuous IV infusion, initially. Titrate by 0.5 mcg/kg/minute every 5 minutes until desired effect or blood pressure cannot be further reduced without compromising organ perfusion. Max: 10 mcg/kg/minute for 10 minutes.
  • ACE inhibitors ^c131
    • Enalaprilat ^c132
      • Enalaprilat Solution for injection; Neonates, Infants, Children, and Adolescents: 5 to 10 mcg/kg/dose IV every 8 to 24 hours (determined by blood pressure readings) (Max: 1.25 mg/dose).
      • Enalaprilat Solution for injection; Adults: 1.25 to 5 mg IV every 6 hours.

Nondrug and supportive care

Comorbidities

• Hypertension ^c142
  • Uncontrolled hypertension can propagate aortic dissection
  • Ability to control hypertension may influence treatment choice in type B aortic dissection
    • Conservative management is reasonable only if systolic blood pressure can be controlled and maintained at goal
      • Less than 140/90 mm Hg (European aortic diseases guidelines) ^r7
      • Less than 140/90 mm Hg (patients without diabetes) or less than 130/80 mm Hg (patients with diabetes or chronic renal disease) (American aortic diseases guidelines) ^r3

Special populations

• Pregnancy ^r12
  • Survival rate for aortic dissection during pregnancy is 20% to 30%
  • Aortic dissection usually occurs in third trimester
  • Marfan syndrome is present in up to half of pregnancy-associated cases of aortic dissection
  • Beyond 30 weeks’ gestation, emergency cesarean delivery and subsequent cardiac surgery may be the best option to save the lives of both baby and mother

At-risk populations ^r14

• Patients with bicuspid aortic valve
• Patients with known genetic conditions
  • Marfan syndrome
  • Loeys-Dietz syndrome
  • Ehlers-Danlos syndrome
  • Familial aneurysmal and dissection syndromes
  • Turner syndrome
• First-degree relatives of patients with thoracic aortic aneurysm or dissection
• Recent aortic manipulation
• Aortic aneurysm

Screening tests

• Genetic testing and counseling is recommended for: ^r3c164
  • First-degree relatives of a patient with known thoracic aortic aneurysm or dissection ^c165c166
  • First-degree relatives of a patient with known genetic mutation associated with thoracic aortic aneurysm or dissection; after genetic testing and counseling, only the relatives with the genetic mutation should undergo aortic imaging ^{c167c168c169c170}
• Aortic imaging (choice of test per recommendation of cardiologist or cardiothoracic surgeon consultant) and surveillance is recommended for: ^{r3c171c172c173}
  • Patients with thoracic aortic aneurysm ^c174c175c176
  • Patients with bicuspid aortic valve ^c177c178c179
  • Patients with known genetic syndromes associated with thoracic aortic aneurysm and/or dissection
    • Marfan syndrome ^c180c181c182
      • Echocardiogram is recommended at time of diagnosis of Marfan syndrome to determine diameters of aortic root and ascending aorta ^r3
      • Repeat at 6-month intervals to determine rate of enlargement of aorta; if stable, can decrease to annual imaging ^r3
      • If maximal aortic diameter is 4.5 cm or more, or if aortic diameter shows significant growth from baseline, obtain additional imaging ^r3
    • Loeys-Dietz syndrome or another confirmed (non-Marfan) genetic mutation known to predispose to aortic aneurysms and aortic dissections ^c183c184c185
      • Complete aortic imaging at initial diagnosis ^r3
      • Repeat at 6-month intervals to determine if enlargement is occurring ^r3
      • Patients with Loeys-Dietz syndrome should have yearly imaging from cerebrovascular circulation to pelvis ^r3
    • Turner syndrome ^c186c187c188
      • Baseline imaging of heart and aorta for evidence of bicuspid aortic valve, coarctation of aorta, or dilation of ascending thoracic aorta ^r3
      • If initial imaging findings are normal and there are no risk factors for aortic dissection, obtain repeated imaging every 5 to 10 years or if otherwise clinically indicated ^r3
      • If abnormalities exist, obtain annual imaging or follow-up imaging ^r3
  • First-degree relatives of patients with thoracic aortic aneurysm and/or dissection to identify those with asymptomatic disease ^{r3c189c190c191c192c193c194}
    • Imaging of second-degree relatives is reasonable if 1 or more first-degree relatives of a patient with known thoracic aortic aneurysm and/or dissection are found to have thoracic aortic dilation, aneurysm, or dissection