Key Definitions:

• Aneurysm is defined by dilation of the entire vessel wall thickness.
• Dissection occurs when blood enters and separates layers of the vessel wall.

• Both are the result of weak vessel walls, which can result from acquired and/or genetic defects.
• Both can also lead to vessel rupture or other complications.

Review of Aortic Anatomy:

• The aorta arises from the heart as the ascending aorta, then arches posteriorly, and then descends through the trunk, bifurcating to form the common iliac arteries at the pelvis.
  — The descending aorta can be subdivided by the diaphragm: superiorly is the thoracic diaphragm, inferiorly is the abdominal diaphragm.

Aortic aneurysms:

• Vessel wall weakening is due to loss of vascular smooth muscle cells, elastic fibers, and collagen fibers, which are crucial for vessel wall support.
• These deficits may be due to a variety of causes, including atherosclerosis, hypertension, trauma, vasculitis, infections (which cause “mycotic” aneurysms), congenital connective tissue defects, and various genetic factors that predispose an individual to weak vessels.
• Types:
  — Saccular aneurysm consists of asymmetrical outpockets (“sacs”) of the vessel wall.
  — Fusiform aneurysms produce symmetrical dilations – you may recall that “fusiform” means “spindle-shaped,” which describes this morphology.
  — Pseudo-aneurysm/false aneurysm Is not an aneurysm; occurs when a tear in the layers of the vessel wall allows blood to leak through and form a thrombus under the adventitia or surrounding tissues; these are often due to trauma.
• Complications:
  — Ischemia, thromboembolism, dissection, and rupture.

Thoracic aortic aneurysms

• Generally defined as dilations more than 50% of the normal diameter.
• Thoracic aneurysms are associated with genetic disorders that lead to cystic medial necrosis (also called cystic medial degeneration), including Marfan, Loeys-Dietz, and Ehlers-Danlos syndromes.
  — Cystic medial necrosis is characterized by abnormal smooth muscle cells and elastic fibers, with
  “cyst-like” areas of ground substance; because necrosis is not always present, many authors prefer the term “cystic medial degeneration.”
• Thoracic aneurysms are often asymptomatic, but, show that they can compress surrounding tissues and cause chest or back pain, coughing, and dysphagia (difficulty swallowing).

Abdominal aortic aneurysms

• Typically defined as dilations larger than three centimeters.
• They are also usually asymptomatic, but can compress surrounding structures to produce abdominal or back pain. In some patients, a “pulsatile” mass may be present.
• Abdominal aneurysms are associated with smoking, family history of abdominal aneurysm, hypertension, and atherosclerosis.
  — They most commonly occur in males over 65 years; in women, they tend to occur later in life and with worse prognosis.
  — Because the standard definition of an abdominal aneurysm as dilations greater than 3 cm is based on male anatomy, some authors question whether this threshold is appropriate for women, and, whether this definition may lead to underdiagnosis.

• Treatment for aortic aneurysm is geared towards prevention of dissection and rupture, and includes monitoring for aneurysm enlargement, lowering blood pressure, and, where necessary, surgical intervention.

Aortic Dissection

• Dissection occurs when a tear in the tunica intima allows blood to move between the wall layers; indicate that the area where the blood now flows is called a “false channel” or “false lumen.”
• Dissection can produce a sharp “tearing” pain, which may be mistaken for myocardial infarction.
• Complications include aortic valve regurgitation, cardiac tamponade, and internal bleeding, as well as rupture.

4 types of Aortic Dissection
Let’s illustrate four types of aortic dissection, which are categorized via two overlapping systems: the Stanford and DeBakey systems. These systems can be used for treatment and prognostic assessments.
Proximal

• Proximal tears produce Stanford Type A and DeBakey Types I and II dissections:
  — Tears occur in the ascending portion of the aortic arch, and blood can leak through and move along the length of the aorta or remain in the ascending portion.
  Distal
• Tears distal to the left subclavian artery produce Stanford Type B and DeBakey Types IIIa and IIIb: blood can travel as distally as the diaphragm or leave the thoracic cavity and extend all the way down the aorta.

As a simple way to remember this, think of Type A as Proximal, which comes before Type B, which is Distal.

Aortic Rupture

• Can result from aneurysms and/or dissection; it can also occur as the result of trauma, such as motor vehicle accidents.
• Rupture constitutes a medical emergency, since hemorrhaging and shock can be fatal.
• Fluoroquinolones, which are broad-spectrum antibiotics, have been shown to increase the risk of aortic rupture in vulnerable patients (those with hypertension and aneurysms, for example); thus, alternative treatments should be sought in these cases.

BACTERIAL PATHOGENS

Account for the majority of infective endocarditis cases – approximately 98%.

Gram Positive – 80% of cases

Staphylococcus is a major cause of both health care and community acquired endocarditis

• Staphylococcus is a normal inhabitant of the human nares, pharynx, and skin.
• S. aureus is the most common and virulent cause of IE; it causes acute, flu-like symptoms, and antibiotic resistant strains are increasingly common, even outside of hospital settings. “Aureus” means “golden”; on blood agar plates, S. aureuscolonies produce a golden color. It occurs in “grape-like” clusters.
  – It is coagulase-positive, which means that it produces enzymes that promote blood clotting.
• Coagulase-negative strains (CoNS) of Staphylococcus contribute to the normal flora of the skin and mucosal membranes; two strains relevant to IE are:
  – S. epidermis, found on the skin, is specifically associated with prosthetic valve infective endocarditis and health-care associated IE.
  – S. lugdunesis infection is rare, but aggressive with a high mortality rate.

Streptococcal strains

• Viridans group, which is a normal component of the flora of the oropharynx, urogenital and gastrointestinal systems.
  – Specifically, S. salivarius, S. mitis, and S. sanguinis are associated with endocarditis (be aware of intertextual variation regarding the exact species);
  – Viridans group streptococci comprise the second most common cause of IE, but, unlike S. aureus, are associated with subacute infection.
• S. pneumoniae, which is associated with prosthetic valve IE; alcoholism is a risk factor for this type of infection (some include S. pneumoniae in the Viridans group).
• S. gallolyticus (formerly S. bovis) can cause subacute IE; this pathogen is commonly found in the gastrointestinal tract, and is associated with increased risk of colon cancer.

Enterococci

• E. faecailis and E. faecium comprise the third most common cause of IE; they are part of the normal flora of the colon, and cause subacute IE.
  – Use of broad-spectrum antibiotics increases the risk of Enterococci infection, and hospital-associated infections are on the rise.

Other

• Tropheryma whipplei, which is the causative agent of Whipple’s disease; this pathogen should be considered when culture-negative endocarditis is suspected.
• Erysipelothrix rhusiopathiae is an example of a zoonotic pathogen; it tends to affect the aortic valve, and is associated with a high mortality rate.
• Species of Corynebacterium tend to infect prosthetic devices.

Gram-negative bacterial – account for 1-10%

Can be categorized as HACEK or non-HACEK.

HACEK strains
Tend to have low virulence, and are associated with subacute cases and are characterized by Osler’s nodes (tender, painful nodes on the tips of the fingers or toes).
Research suggests that HACEK infection is more common in younger individuals, particularly males, and those with mechanical heart valves or diabetes; there is evidence that stroke risk is increased with HACEK infections.
The HACEK strains:

• Haemophilus species are the HACEK strains most likely to cause IE; they tend to affect the aortic and mitral valves, specifically.
• Aggregatibacter species are slower to grow, and tend to appear in individuals with underlying valve damage.
• Cardiobaceterium hominis tends to affect those with underlying heart disease, and appears on the mitral and aortic valves.
• Eikenella corrodens, a strain associated with intravenous drug use and/or pre-existing valve disease.
• Kingella kingae, which is associated with the aortic and mitral valves can progress rapidly.

Non-HACEK
Rarely the cause of endocarditis; but, when they are, tend to be associated with health care settings and individuals with implanted devices.
Their rarity can lead to delayed diagnosis, and, consequently, increased risk of complications such as embolization.
Relevant strains:

• Bartonella species, particularly B. quintana and B. henselae, tend to affect the aortic valve; they produce subacute infection, and should be a consideration where culture-negative endocarditis is suspected.
• Coxiella burnetti-induced endocarditis is a complication of Q fever; it is a zoonotic infection spread via spores, and should be considered in cases of culture-negative endocarditis.
• Enterobacteriaceae species infection is rare, but very severe; infection occurs in immunocompromised individuals and those with valvular heart disease.
• Pseudomonas aeruginosa is associated with severe infection in immunocompromised hosts, and is resistant to antibiotics; not surprisingly, then, it is associated with a high mortality rate.

FUNGAL PATHOGENS

Fungal pathogens are rare causes of endocarditis; they account for approximately 2 percent of IE cases.
Fungal pathogens are opportunistic, and form large, warty vegetations; infections are associated with a high mortality rate.
Two key species are:

• Candida, particularly C. albicans, is a yeast that tends to infect cardiac devices, and is associated with intravenous drug use; complications include loss of vision and cutaneous nodules.
• Aspergillus is a ubiquitous mold; infection is associated with hemorrhagic black skin lesions, vascular invasion, and tissue necrosis.

DIAGNOSIS

Modified Duke criteria

Pathological criteria:

• Evidence of micro-organisms in a vegetation, in a vegetative embolus, and/or within an intracardiac abscess.

Clinical criteria are distinguished as major or minor:

• Major criteria include:
  – Positive blood cultures of a characteristic pathogen or consistently positive for a lesser-common pathogen.
  – Echocardiographic evidence of vegetative masses or abscesses.

• Minor criteria include:
  – Predisposing heart condition or intravenous drug use
  – Fever
  – Vascular phenomena (for example, Janeway’s lesions, which are small nodular lesions on the palms of the hands or soles of the feet)
  – Immunological phenomena (for example, Osler’s nodes, glomerulonephritis, or Roth spots)
  – Microbiologic evidence that does not meet Major criteria standards (for example, a single positive culture for an uncommonly associated organism)
  – Echocardiographic evidence that is consistent with, but not diagnostic of, endocarditis (for example, worsening of a heart murmur).

• Clinical diagnosis of IE requires one of the following:
  – The presence of 2 major criteria
  – The presence of 1 major and 3 minor criteria
  – The presence of 5 minor criteria