User:Chelseavallone/Familial Aortic Dissection

Introduction
Familial Aortic Dissection (FAD) is mainly a genetically based disease of weakened aortic connective tissue, however there is controversy over the mode of inheritance and the gene(s) involved. Over time this weakness, along with systolic pressure, results in a tear in the aortic intima layer thus allowing blood to enter between the layers of tissue and cause further tearing. Eventually complete rupture of the aorta occurs and the pleural cavity fills with blood. Warning signs include chest pain, ischemia, and hemorrhaging in the chest cavity. This condition, unless found and treated early, usually results in death. Immediate surgery is the best prognosis in most cases. FAD is not to be confused with PAU (penetrating atherosclerotic ulcers) and IMH (intramural hematoma), both of which present in ways similar to that of familial aortic dissection. Acutely, aortic dissection is the most common disease of the aorta. If left untreated, three quarters of those infected will die within two weeks of an aortic episode. Because of this, early detection is key.

Characteristics
Normally associated with Marfan syndrome and various other genetic disorders which affect the connective tissues, the layers of lumen that compose our arteries and veins become loose. Once loose these areas become susceptible to minor tears. Blood then begins to pool within these tears causing bulging of the ascending or descending aorta. This creates a false lumen that is very noticeable and easily recognizable as the most common characteristic for diagnosis. In some cases it is not uncommon to see malfunctioning in the atrioventricular and semilunar valves. Depending on the extent of pooling and damage to the blood vessel, the Svensson system is used to describe the five classes of pathological processes that may b visible due to the dissection. Class 1 is any dissection with a true and false lumen. Class 2 depends on the presence of hematomahematoma or hemorrhaging. Class 3 is a dissection without hematoma. Class 4 is recognized by the presence of an ulcer. Class 5 has to do with any sort of traumatic hemorrhaging in the dissection. Those experiencing aortic dissection typically will complain of agaonizing pains described with a ripping feeling in the chest that for some may migrate to their backs.

Causes
Inheritance is thought to be rather complex. There is a good amount of evidence that shows the disease is autosomal dominantautosomal dominant, with some penetrance. There is also the possibility of age related dependence. It is known that Marfan’s Syndrome and Ehler-Danlos Syndrome lead to an increased risk for development of FAD. Marfan’s Syndrome is not required to have an aortic dissection. One study suggests that the chromosomal locus for the gene is 5q13-14. The same study found that other genes may be linked, and include loci for Marfan and Ehler-Danlos Syndromes, genes for metalloproteinase 3 and 9, and tissue inhibitor of malloproteinase 2 as well as two loci on chromosomes 5q13-14 and lq23.2-24.(2) Still other studies show that mutations in smooth muscle cell-specific isoforms of alpha actinactin and beta myosin heavy chain may cause FAD. Mutations in the genes TGFBR 1 and 2 are known to cause dissecions in aortas with normal diameter size (>4.3cm.) and gene FPN1 mutations typically affect aortas with larger diameters (<4.4cm.).

There are several hypotheses which attempt to explain how the dissection physically occurs. The first states that a tear develops in the intima layer of the aorta which allows blood to flow from the lumen of the aorta into the intima. This event creates a dissection and essentially two lumens. The second hypothesis suggests that the vasa vasorum ruptures and causes a hemorrhage in the wall of the aorta. The hemorrhaging promotes tearing of the intima and eventually aortic dissection.

The major risk factors for FAD include high blood pressure, old age, haematoma, genetic weakening of aortic wall, cocaine use, pregnancy and diseases causing abnormal connective tissue. One study found that the average age(s) for the occurrence of dissection caused by degenerative anuerysm is 65 years and up. Dissections thought to be the result of genetic mutations appear to be more likely to occur between the ages of 40 and 60. Another study found that 20% of patients with FAD have a close relative with a history of thoracic aortic aneurysm or dissection which suggests yet another major risk factor.

Diagnosis
Since the cause of FAD has not been genetically pinpointed, the only way to diagnose FAD is through the examination of phenotypic variations in the aorta. Usually echocardiography is used to take measurements of the aortic root as well as transesophageal echocardiography echocardiography. Biomarkers lend a quick way to diagnose dissecion when time is of the essence. These have the ability to relay the levels of smooth muscle mysosin heavy chain protein present, which is released from damaged aortic tissue.

There are two types of FAD; groups A and B. Normally if any area of the ascending aorta is involved in the dissection this is considered group A. If the dissection occurs within the descending aorta this is classified in group B. These two groups can than be broken down into three classes of FAD: Type 1, Type 2 and Type 3. Group A consists of Types 1 and 2, whereas Group B consists only of Type 3. Type 1 encompasses dissection in the distal ascending aorta closes to the heart, not including the aortic arch. Type 2 refers to dissection of the ascending aorta, closer to and including the aortic arch. Type 3 refers to the descending thoracic and abdominal aorta.

Group A dissections are the more serious of the two due to the location of the dissection in the ascending aorta, which leads to a higher risk of congestive heart failure and pericardium and/or aortic valve rupture. Indiviuals also tend to be predisposed to type A if they do have Marfans or Elhers-Danlos syndromes. Theses contribute to a higher fatality rate in group A dissection if immediate surgery is not preformed. The most common corrective surgeries are actual aortic valve replacement and coronary artery bypass. The five year survival rate after surgery is a successful 70.4% due to vigilant monthly physical exams and chest x-rays to moniter progress. Group B dissections typically have a higher surgery mortality rate and are therefore not good canidates. Instead medical mangagement is the common response to treating and keepind dissections of the descending aorta under control.

Treatment
Type 1 and Type 2 FAD call for the same treatment: immediate surgery to replace the aorta. Surgery is required due to the high risk of mortality. Type 3 is less severe and requires the maintenance of blood pressure through diet and exercise. Upon diagnosing someone with FAD intravenous antihypertensive treatmentis frequently used. Often intravenous sodium nitroprusside is used for it's efficiency in lessening the pulsatile load thus reducing blood pressure. Reducing this force slows the progression of the dissection. Surgical success depends on age, severity of symptoms, postoperative organ dysfunction and stroke. Surgical intervention is always indicated in Type 1 cases. Aortic surgery is palliative, not curative. The goal is to merely to prevent rupture, restore blood flow, and fix any aortic valve disfunction. Post operative protocals include frequent monitoring of the aorta diameter. Statins and beta blockers are also popular treatments used to reduce future plaque build up and blockage of epinephrine receptors as a way to control heart rate and blood pressure.

Long term treatment should also include regular check ups every 3 to 6 months. A CT scan, MRI, or TEE is recommended, along with required chest x-rays. Antihypertensive therapy with beta adrenergic antagonists is required regardless of medical versus surgical treatment. Ten to twenty percent of those who choose surgical intervention are re-operated on due to compression, aneurysm development or blood leakage.

Current Topics
Currently, there is controversy over whether or not inheritance truly plays a role in FAD, and if so which gene it acts upon. FAD does not come from strictly one predisposing factor, such as hypertension. It is suggested that the combination of environmental factors along with genetics may contribute to causing FAD. Before newer and more effective cures and therapies can be developed, first the specific gene mutation must be identified. Until such a gene is determined, scientists say patient education, and physician awareness is vital. Currently scientists have found animal models to be beneficial in understanding the pathology behind FAD. In the future they hope to develop drugs that will better support and strengthen the aortic wall. Endovascular methods of treatment are becoming increasingly popular, and scientists hope to use this technique in both acute and chronic cases.

Contributions
'''Chelsea V- Treatment, Stats, Diagnosis '''Beth S- Causes and Stats '''Kelly B- Treatment, Introduction, Current Topics Dave K- Characteristics and Diagnosis. '''