Aortic Dissection/Marfan Syndrome Case File

Aortic Dissection/Marfan Syndrome Case File

Eugene C. Toy, MD, Gabriel M. Aisenberg, MD

Case 5

A 42-year-old man is brought to the emergency department (ED) by ambulance after a sudden onset of severe retrosternal chest pain that began one hour ago while he was at home mowing the lawn. He initially described the pain as a tearing sensation that is now sharp, constant, referred to his back, and unrelated to movement. Three doses of sublingual nitroglycerin administered by the paramedics while en route to the hospital did not relieve the pain. He has never had symptoms like this before. His only medical history is hypertension, for which he takes enalapril. There is no cardiac disease in his family. He does not smoke, drink alcohol, or use illicit drugs. He is a basketball coach at a local high school and is usually very physically active.

On physical examination, he is a tall man with long extremities, appearing uncomfortable and diaphoretic while lying on the stretcher with his eyes closed. He is afebrile, with a heart rate of 118 beats per minute (bpm) and blood pressure of 156/64 mm Hg in the right arm and 188/74 mm Hg in the left arm. His head and neck examinations are unremarkable. His chest is clear to auscultation bilaterally, and an incidental note is made of pectus excavatum. His heart rate is tachycardic and regular. A soft, early diastolic murmur is auscultated at the right sternal border with bounding pulses. His abdominal examination is benign, and neurologic examination is nonfocal. His chest x-ray shows a widened mediastinum.

▶ What is the most likely diagnosis?

▶ What is your next step?

ANSWERS TO CASE 5:

Aortic Dissection/Marfan Syndrome

Summary: A 42-year-old tall man with pectus excavatum presents with

• Severe chest pain unrelieved by nitroglycerin
• Asymmetrically elevated blood pressure in his arms
• New murmur of aortic insufficiency
• Chest x-ray that shows a widened mediastinum

Most likely diagnosis: Aortic dissection, likely secondary to Marfan syndrome.

Next step: Administer an intravenous beta-blocker to lower blood pressure and arterial shear stress, then perform a noninvasive imaging procedure, such as transesophageal echocardiography (TEE), computed tomography (CT) angiography, or magnetic resonance angiography (MRA).

ANALYSIS

Objectives

1. Understand the clinical and radiographic features of aortic dissection as well as complications of dissection. (EPA 3)
2. Identify the risk factors for aortic dissection. (EPA 1, 2, 7)
3. Identify common genetic syndromes associated with aortic dissection. (EPA 2, 12)
4. Understand the management of dissection and the indications for surgical versus medical treatment. (EPA 4, 10)
5. Recognize other aortic diseases, such as abdominal aortic aneurysm (AAA), and the role of surveillance and indications for surgical repair. (EPA 1, 4, 7, 10)

Considerations

Most patients with chest pain seek medical attention because of the concern about myocardial infarction (MI). Differentiating other conditions of chest pain is important because some underlying conditions, such as aortic dissection, could be worsened by an MI treatment algorithm, for example, by anticoagulation with heparin or use of thrombolytics. In hypertensive patients with dissection, urgent blood pressure lowering is indicated to limit propagation of the dissection.

The aorta is the largest conductance vessel in the body. It receives most of the shear forces generated by the heart with every heartbeat throughout the lifetime of an individual. The wall of the aorta is composed of three layers: the intima, the media, and the adventitia. These specialized layers allow the aortic wall to distend under the great pressure created by every heartbeat. The vessel walls expand and accommodate the forward flow of blood ejected from the heart during each cardiac cycle, thus storing kinetic energy as potential energy and creating large amounts of tensile stress. Pathologic processes arise when the vessel wall is unable to accommodate this tension.

APPROACH TO:

Aortic Aneurysm and Dissection

DEFINITIONS

AORTIC ANEURYSM: Defined as a pathologic dilation of more than 1.5 times the normal diameter of the aorta. Aneurysms can occur anywhere in the thoracic or abdominal aorta, but the large majority occur in the abdomen, below the renal arteries and above the bifurcation of the iliac vessels.

AORTIC DISSECTION: Tear or ulceration of the aortic intima that allows pulsatile aortic flow to dissect longitudinally along elastic planes of the media, creating a false lumen or channel for blood flow.

CLINICAL APPROACH TO AORTIC DISSECTION

Epidemiology

Cystic degeneration of the elastic media predisposes patients to aortic dissection. This occurs in various connective tissue disorders that cause cystic medial degeneration, such as Marfan syndrome and Ehlers-Danlos syndrome. Examine for characteristic features of Marfan, including tall stature, long extremities, joint hypermobility, pectus deformity, and scoliosis. Other genetic syndromes and gene mutations may accelerate development of aneurysms and dissection and are described in Table 5–1.

Other factors predisposing to aortic dissection are hypertension, aortic valvular abnormalities such as aortic stenosis and congenital bicuspid aortic valve, coarctation of the aorta, the third trimester of pregnancy, atherosclerotic disease, vasculitis, amphetamines/cocaine, and trauma. Aortic dissection may also occur iatrogenically after cardiac surgery or catheterization. More recently, the use of fluoroquinolones has been associated with an increased risk of aneurysm and dissection; care should be taken to choose alternative antibiotic regimens, if possible. Causes are outlined in Table 5–2.

Pathophysiology

A dissection occurs when there is a sudden intimal tear or rupture followed by the formation of a dissecting hematoma within the aortic media, separating the intima from the adventitia and propagating distally. The presence of hypertension and associated shear forces is the most important factor causing propagation of the dissection. Aortic dissection can produce several devastating or fatal complications. It can produce an intraluminal intimal flap, which can occlude branch arteries and cause organ ischemia or infarction. The hematoma may rupture into the pericardial sac, causing cardiac tamponade, or into the pleural space, causing hemothorax

aOther genes that have been implicated in nonsyndromic arterial dissection include TAAD1, FAA1, TAAD2, and MYH11.

and/or exsanguination. It can produce severe acute aortic regurgitation, leading to fulminant heart failure.

Clinical Presentation

Clinical features typically include a sudden onset of ripping or tearing chest pain, radiating to the back. However, the pain may radiate to the neck or extremities as the dissection extends (Table 5–3). Differentiating the pain of dissection from the pain of myocardial ischemia or infarction is essential because the use of anticoagulation or thrombolytics in a patient with a dissection may be devastating. In contrast to anginal pain, which often builds over minutes, the pain of dissection is often maximal at onset. In addition, myocardial ischemia pain is usually relieved by nitrates, whereas the pain of dissection is not. Also, because most dissections begin very close to the aortic valve, a dissection may produce an early diastolic murmur characteristic of aortic insufficiency. If it occludes aortic branch arteries, such as the brachiocephalic artery, it can produce dramatically different pulses and blood pressures in the extremities. Most patients with dissection are hypertensive; if hypotension is present, one must suspect aortic rupture, cardiac tamponade, or dissection of the subclavian artery supplying the arm where the blood pressure is being measured. Often, a widened superior mediastinum (> 8 cm) is noted on plain chest film because of dissection of the ascending aorta.

Diagnostic Approach. When aortic dissection is suspected, confirming the diagnosis with an imaging study is essential. Conventional aortography was the traditional diagnostic “gold standard,” but in recent years, very sensitive noninvasive studies, such as TEE, dynamic CT scanning, and magnetic resonance imaging (MRI), have gained widespread use. Because of the emergent nature of the condition, the best initial study is the one that can be obtained and interpreted quickly in the given hospital setting. If the patient is hemodynamically unstable or has renal insufficiency, TEE is the best test. Otherwise, CT angiography is widely used.

Classification. Several classification schemes describe the different types of aortic dissections. Figure 5–1 shows the Stanford classification. Type A dissection

Figure 5–1. Classification of aortic aneurysms. (Reproduced with permission, from Braunwald E,

Fauci AS, Kasper KL, et al. Harrison’s Principles of Internal Medicine. 17th ed. 2008. Copyright © McGraw Hill LLC. All rights reserved.)

always involves the ascending aorta but may extend to any other part. Type B dissection does not involve the ascending aorta. The alternative method of classification, the DeBakey classification scheme, splits type A dissections into types 1 and 2 and splits type B dissections into types 3a and 3b.

Treatment

Two-thirds of aortic dissections originate in the ascending aorta only centimeters above the aortic valve. The classification system is important because it guides therapy. Virtually all type A (proximal or ascending) dissections require urgent surgical therapy with replacement of the involved aorta and sometimes the aortic valve. Without surgery, the mortality rate for type A dissections is 90%. Type B dissections do not involve the ascending aorta and typically originate in the aortic arch distal to the left subclavian artery. Usually, type B dissections are first managed medically, with surgery reserved only for complications such as rupture or ischemia caused by occlusion of an aortic branch.

The aim of medical therapy is to prevent propagation of the dissection by reducing mean arterial pressure and the rate of rise (dP/dT) of arterial pressure, which correlates with arterial shear forces. Beta-blockers (ie, metoprolol, esmolol, labetalol) are used as first-line treatment to lower systolic blood pressure to < 120 mm Hg and achieve a heart rate of 60 bpm, ultimately reducing shear forces. If hypertension is refractory, sodium nitroprusside may be used; it is generally not used initially due to risks of causing cyanide toxicity, especially in patients with renal insufficiency.

CLINICAL APPROACH TO ABDOMINAL AORTIC ANEURYSMS

Epidemiology

Abdominal aortic aneurysms are found in 1.5% to 3% of older adults but in 5% to 10% of higher risk patients, such as those with known atherosclerotic disease. AAA is a degenerative condition typically found in older white men (> 50 years), most commonly in smokers, who often have atherosclerotic disease elsewhere, such as coronary artery disease or peripheral vascular disease. Smoking has been found to be the most significant risk factor for the development of AAAs. Thus, it is recommended that men between the ages of 65 and 75 who have a history of smoking should be screened for AAA with ultrasound.

Pathophysiology

In marked contrast to the dramatic presentation of dissection of the thoracic aorta, patients with AAA are typically asymptomatic; AAAs are often found by physical examination with detection of a midline pulsatile mass and auscultation of an abdominal bruit or noted incidentally on imaging (ie, ultrasound). AAA is usually defined as a dilation of the aorta with a diameter greater than 3 cm, typically below the renal vasculature and above the bifurcation of the common iliacs.

One complication of AAAs is atheroembolic disease—small thrombi may form within the aneurysm due to turbulent blood flow and can embolize to extremities, leading to signs of distal ischemia. Findings can range from blue toe syndrome to livedo reticularis. However, the feared complication of AAA is spontaneous rupture, which can be visualized with ultrasound or contrast CT. If AAA ruptures anteriorly into the peritoneal cavity, the patient usually exsanguinates and dies within minutes. If AAA ruptures posteriorly and the bleeding is confined to the retroperitoneum, the peritoneum can produce local tamponade, and the patient will present with severe lower back or midabdominal pain. Skin findings of rupture may include Grey Turner sign, which is ecchymosis of the flank, and Cullen sign, which is periumbilical ecchymosis. Overall, the mortality rate of ruptured AAA is 80%, with 50% of patients dying before they reach the hospital. The risk of rupture is related to the size of the aneurysm: The annual rate of rupture is low if the aneurysm is smaller than 5 cm but is at least 10% to 20% for 6-cm aneurysms.

Treatment

The risk of rupture must be weighed against the surgical risk of elective repair, which traditionally requires excision of the diseased aorta and replacement with a Dacron graft, although endovascular treatment with placement of an aortic stent graft is now commonly performed. Operative repair of AAAs is indicated for aneurysms 5.5 cm or greater in diameter, aneurysms expanding more than 1 cm per year, or symptomatic aneurysms. Postoperative complications may include bowel ischemia, infection, and rarely, aorto-enteric fistula. As for surveillance of AAAs, the current recommendations are that patients undergo some sort of imaging of the aneurysm (MRI, CT scan, or ultrasound study) at 6-month to 3-year intervals, depending on the risk of rupture. Surveillance guidelines are outlined in Table 5–4.

Data from Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018;67(1):2-77.e2.

CASE CORRELATION

• See also Case 3 (Acute Coronary Syndrome), Case 6 (Hypertension, Outpatient), and Case 7 (Hypertensive Encephalopathy/Pheochromocytoma).

COMPREHENSION QUESTIONS

5.1 A 59-year-old man complains of severe chest pain that radiates to his back. His brachial pulses appear unequal between his right and left arms. He appears hemodynamically stable. On chest radiography, he has a widened mediastinum. Which of the following is the best next step?

A. Initiate thrombolytic therapy.

B. Obtain CT of chest with intravenous contrast.

C. Initiate aspirin and heparin.

D. Measure serial cardiac enzyme levels.

5.2 A 45-year-old woman with new-onset aortic regurgitation is found to have aortic dissection of the ascending aorta and aortic arch by TEE. She is relatively asymptomatic. Which of the following is the best management?

A. Oral atenolol therapy and monitor the dissection

B. Angioplasty

C. Surgical repair of the dissection

D. Oral warfarin (Coumadin) therapy

5.3 A healthy 75-year-old man undergoing an ultrasound examination for suspected gallbladder disease is found incidentally to have a 4.5-cm abdominal aneurysm of the aorta. Which of the following is the best management for this patient?

A. Surgical repair of the aneurysm

B. Serial ultrasound examinations every 6 months

C. Urgent MRI

D. Beta-agonist therapy

5.4 A 45-year-old man with a past medical history of diabetes, hyperlipidemia, and hypertension has smoked one pack of cigarettes a day for the past 15 years and drinks four glasses of wine every weekend. He is found to have an AAA incidentally on CT imaging of the abdomen. Which of the following is the most important predisposing factor for the development of his AAA?

A. Hypertension

B. Smoking

C. Hyperlipidemia

D. Alcohol use

ANSWERS

5.1 B. This clinical presentation of severe chest pain radiating to the back, unequal brachial blood pressures or pulse strengths, and a widened mediastinum on chest x-ray is consistent with acute aortic dissection. A CT scan of the chest is a quick imaging test to confirm the aortic dissection. Thrombolytic therapy (answer A) or anticoagulation (answer C) can worsen the process. Measuring serial cardiac enzyme levels (answer D) would only delay the therapy and endanger the patient.

5.2 C. Surgery is urgently required in the event of aortic root or other proximal (type A) dissections. An unrecognized, and hence untreated, aortic dissection can quickly lead to exsanguination and death. Medical therapy such as beta-blockers (answer A) can help to decrease the risk of dissection while getting the patient urgently to the operating room, but a type A dissection should not merely be monitored since it has a very high mortality rate without surgery. Angioplasty (answer B) may be indicated in a case of MI, but not in aortic dissection. Anticoagulation (answer D) is not appropriate in this scenario.

5.3 B. When an AAA reaches 5.5 cm or greater, surgery (answer A) is usually required because of the high risk of aneurysm rupture. For asymptomatic aneurysms smaller than 5 cm, the 5-year risk of rupture is less than 1% to 2%, so serial noninvasive monitoring is an alternative strategy. Further imaging such as with CT or MRI (answer C) is not warranted with the ultrasound diameter being less than the threshold. Answer D (beta-agonist therapy) is indicated when there is aortic dissection, to prepare for intervention, but not in this patient with an indolent and chronic AAA.

5.4 B. Risk factors for AAA include smoking, hypertension (answer A), and peripheral vascular disease. However, the single greatest risk factor for developing AAA is smoking history. Thus, it is recommended that all men with a history of smoking undergo a one-time screening for AAA between the ages of 65 and 75. Although hyperlipidemia (answer C) and alcohol use (answer D) are risk factors for the development of AAA, these factors are not as strongly associated with AAA as smoking.

    CLINICAL PEARLS    

▶ Hypertension is an underlying factor that predisposes to aortic dissection in most cases. Other patients at risk include those with Marfan syndrome, patients with congenital aortic anomalies, or otherwise normal women in the third trimester of pregnancy.

▶ Chest pain in the presence of a widened mediastinum on chest x-ray should suggest aortic dissection.

▶ Medical therapy for aortic dissection includes intravenous beta-blockers such as metoprolol, esmolol, or labetalol to lower cardiac contractility, arterial pressure, and shear stress, thus limiting propagation of the dissection.

▶ Urgent surgical repair is indicated for type A (ascending) aortic dissections. Uncomplicated, stable, type B (transverse or descending) aortic dissections can be managed medically.

▶ Aortic dissection may be complicated by rupture, occlusion of any branch artery of the aorta, or retrograde dissection with hemopericardium and cardiac tamponade.

▶ Men between the ages of 65 and 75 with a smoking history should be screened for AAA by ultrasound.

▶ The risk of rupture of AAAs increases with size. Aneurysms larger than 5.5 cm should undergo elective surgical repair; those smaller than 5.5 cm can be monitored with serial ultrasonography.

REFERENCES

Blanchard JF, Armenian HK, Friesen PP. Risk factors for abdominal aortic aneurysm: results of a case-control study. Am J Epidemiol. 2000;151(6):575-583. 

Caglayan AO, Dundar M. Inherited diseases and syndromes leading to aortic aneurysms and dissections. Eur J Cardiothorac Surg. 2009;35(6):931-940. 

Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018;67(1):2-77.e2. 

Creager MA, Loscalzo J. Diseases of the aorta. In: Jameson JL, Fauci AS, Kasper D, et al, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw Hill; 2018:2060-2066. 

Erbel R, Alfonso F, Boileau C, et al. Diagnosis and management of aortic dissection. Eur Heart J. 2001;22:1642-1681. 

Lee CC, Lee MT, Chen YS, et al. Risk of aortic dissection and aortic aneurysm in patients taking oral fluoroquinolone. JAMA Intern Med. 2015;175(11):1839-1847. 

Powell JT, Greenhalgh RM. Clinical practice: small abdominal aortic aneurysms. N Engl J Med. 2003;348:1895-1901.

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