Quadricuspid aortic valves are very rare cardiac valvular anomalies with a prevalence of 0.013% to 0.043% of cardiac cases and a prevalence of 1 in 6000 patients that undertake aortic valve surgery. There is a slight male predominance in all of the cases, and the mean age is 50.7.

Several genetic causes of Loeys–Dietz syndrome have been identified. A "de novo" mutation in TGFB3, a ligand of the TGF ß pathway, was identified in an individual with a syndrome presenting partially overlapping symptoms with Marfan Syndrome and Loeys-Dietz Syndrome.

The following table includes the main types of valvular stenosis and regurgitation. Major types of valvular heart disease not included in the table include mitral valve prolapse, rheumatic heart disease and endocarditis.

When treated early, that is, before the onset of pulmonary hypertension, a good outcome is possible in patients with Shone’s syndrome. However, other surgical methods can be employed depending upon the patient’s medical background. The single most important determinant of poor outcome during the surgical management of patients with Shone's syndrome is the degree of involvement of the mitral valve and the presence of secondary pulmonary hypertension.

Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome. The disorder is marked by aneurysms in the aorta, often in children, and the aorta may also undergo sudden dissection in the weakened layers of the wall of aorta. Aneurysms and dissections also can occur in arteries other than the aorta. Because aneurysms in children tend to rupture early, children are at greater risk for dying if the syndrome is not identified. Surgery to repair aortic aneurysms is essential for treatment.

There are four types of the syndrome, labelled types I through IV, which are distinguished by their genetic cause. Type 1, Type 2, Type 3, and Type 4 are caused by mutations in "TGFBR1", "TGFBR2", "SMAD3", and "TGFB2" respectively. These four genes encoding transforming growth factors play a role in cell signaling that promotes growth and development of the body's tissues. Mutations of these genes cause production of proteins without function. Although the disorder has an autosomal pattern of inheritance, this disorder results from a new gene mutation in 75% of cases and occurs in people with no history of the disorder in their family.

Loeys-Dietz syndrome was identified and characterized by pediatric geneticists Bart Loeys and Harry Dietz at Johns Hopkins University in 2005.

The risk of death in individuals with aortic insufficiency, dilated ventricle, normal ejection fraction who are asymptomatic is about 0.2 percent per year. Risk increases if the ejection fraction decreases or if the individual develops symptoms.

Individuals with chronic (severe) aortic regurgitation follow a course that once symptoms appear, surgical intervention is needed. AI is fatal in 10 to 20% of individuals who do not undergo surgery for this condition. Left ventricle dysfunction determines to an extent the outlook for severity of aortic regurgitation cases.

Inflammation of the heart valves due to any cause is called valvular endocarditis; this is usually due to bacterial infection but may also be due to cancer (marantic endocarditis), certain autoimmune conditions (Libman-Sacks endocarditis, seen in systemic lupus erythematosus) and hypereosinophilic syndrome (Loeffler endocarditis). Certain medications have been associated with valvular heart disease, most prominently ergotamine derivatives pergolide and cabergoline.

Valvular heart disease resulting from rheumatic fever is referred to as "rheumatic heart disease". Damage to the heart valves follows infection with beta-hemolytic bacteria, such as typically of the respiratory tract. Pathogenesis is dependent on cross reaction of M proteins produced by bacteria with the myocardium. This results in generalized inflammation in the heart, this manifests in the mitral valve as vegetations, and thickening or fusion of the leaflets, leading to a severely compromised buttonhole valve.

Rheumatic heart disease typically only involves the mitral valve (70% of cases), though in some cases the aortic and mitral valves are both involved (25%). Involvement of other heart valves without damage to the mitral are exceedingly rare.

While developed countries once had a significant burden of rheumatic fever and rheumatic heart disease, medical advances and improved social conditions have dramatically reduced their incidence. Many developing countries, as well as indigenous populations within developed countries, still carry a significant burden of rheumatic fever and rheumatic heart disease and there has been a resurgence in efforts to eradicate the diseases in these populations.

Individuals with MVP are at higher risk of bacterial infection of the heart, called infective endocarditis. This risk is approximately three- to eightfold the risk of infective endocarditis in the general population. Until 2007, the American Heart Association recommended prescribing antibiotics before invasive procedures, including those in dental surgery. Thereafter, they concluded that "prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis."

Many organisms responsible for endocarditis are slow-growing and may not be easily identified on routine blood cultures (these fastidious organisms require special culture media to grow). These include the HACEK organisms, which are part of the normal oropharyngeal flora and are responsible for perhaps 5 to 10% of infective endocarditis affecting native valves. It is important when considering endocarditis to keep these organisms in mind.

MR Imaging is best suited to evaluate patients with Shone's complex. Routine blood tests should be done prior to cardiac catheterization. The surgeons will repair the mitral valve and al the partial surgical removal of supramitral ring is done. This surgical method is preferred to the valve replacement procedure.

Classifying cardiac lesions in infants is quite difficult, and accurate diagnosis is essential. The diagnosis of Shone’s complex requires an ultrasound of the heart (echocardiogram) and a cardiac catheterization procedure, that is, insertion of a device through blood vessels in the groin to the heart that helps identify heart anatomy.

Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with autosomal dominant inheritance and variable expression. Mutations in the Ras/mitogen activated protein kinase signaling pathways are known to be responsible for ~70% of NS cases.

A person with NS has up to a 50% chance of transmitting it to their offspring. The fact that an affected parent is not always identified for children with NS suggests several possibilities:

1. Manifestations could be so subtle as to go unrecognized (variable expressivity)

2. NS is heterogeneous, comprising more than one similar condition of differing causes, and some of these may not be inherited.

3. A high proportion of cases may represent new, sporadic mutations.

Heterozygous mutations in "NRAS", "HRAS", "BRAF", "SHOC2", "MAP2K1", "MAP2K2", and "CBL" have also been associated with a smaller percentage of NS and related phenotypes.

A condition known as "neurofibromatosis-Noonan syndrome" is associated with neurofibromin.

The risk for untreated LQTS patients having events (syncopes or cardiac arrest) can be predicted from their genotype (LQT1-8), gender, and corrected QT interval.

- High risk (> 50%) - QTc > 500 ms, LQT1, LQT2, and LQT3 (males)

- Intermediate risk (30-50%) - QTc > 500 ms, LQT3 (females) or QTc < 500 ms, LQT2 (females) and LQT3

- Low risk (< 30%) - QTc < 500 ms, LQT1 and LQT2 (males)

A 1992 study reported that mortality for symptomatic, untreated patients was 20% within the first year and 50% within the first 10 years after the initial syncope.

Prior to the strict criteria for the diagnosis of mitral valve prolapse, as described above, the incidence of mitral valve prolapse in the general population varied greatly. Some studies estimated the incidence of mitral valve prolapse at 5 to 15 percent or even higher. One study suggested MVP in up to 35% of healthy teenagers.

Recent elucidation of mitral valve anatomy and the development of three-dimensional echocardiography have resulted in improved diagnostic criteria, and the true prevalence of MVP based on these criteria is estimated at 2-3%. As part of the Framingham Heart Study, for example, the prevalence of mitral valve prolapse in Framingham, MA was estimated at 2.4%. There was a near-even split between classic and nonclassic MVP, with no significant age or sex discrimination. MVP is observed in 7% of autopsies in the United States.

Risk factors for long QT syndrome include the following:

- female sex

- increasing age

- liver or renal impairment

- family history of congenital long QT syndrome

- pre-existing cardiovascular disease

- electrolyte imbalance: especially hypokalemia, hypocalcemia, hypomagnesemia

- concurrent administration of interacting drugs

Anorexia nervosa has been associated with sudden death, possibly due to QT prolongation. It can lead a person to have dangerous electrolyte imbalances, leading to acquired long QT syndrome and can in turn result in sudden cardiac death. This can develop over a prolonged period of time, and the risk is further heightened when feeding resumes after a period of abstaining from consumption. Care must be taken under such circumstances to avoid complications of refeeding syndrome.

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 there is 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.

A 2007 study followed 112 individuals for a mean of 12 years (mean age 25.3, range 12–71). No patient died during follow-up, but several required medical interventions. The mean final heights were 167 and 153 cm for men and women, respectively, which is approximately 2 standard deviations below normal.

In terms of the cause of aortic insufficiency, is often due to the aortic root dilation ("annuloaortic ectasia"), which is idiopathic in over 80% of cases, but otherwise may result from aging, syphilitic aortitis, osteogenesis imperfecta, aortic dissection, Behçet's disease, reactive arthritis and systemic hypertension. Aortic root dilation is the most common cause of aortic insufficiency in developed countries. Additionally, aortic insufficiency has been linked to the use of some medications, specifically medications containing fenfluramine or dexfenfluramine isomers and dopamine agonists. Other potential causes that affect the valve directly include Marfan syndrome, Ehlers–Danlos syndrome, ankylosing spondylitis, and systemic lupus erythematosus. In acute cases of aortic insufficiency, the main causes are infective endocarditis, aortic dissection or trauma.

Aortic dissection is associated with hypertension (high blood pressure) and many connective tissue disorders. Vasculitis (inflammation of an artery) is rarely associated with aortic dissection. It can also be the result of chest trauma. About 72 to 80% of individuals who present with an aortic dissection have a previous history of hypertension. Illicit drug use with stimulants such as cocaine and methamphetamine is also a modifiable risk factor for AD.

A bicuspid aortic valve (a type of congenital heart disease involving the aortic valve) is found in 7–14% of individuals who have an aortic dissection. These individuals are prone to dissection in the ascending aorta. The risk of dissection in individuals with bicuspid aortic valve is not associated with the degree of stenosis of the valve.

Connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys–Dietz syndrome increase the risk of aortic dissection. Similarly, vasculitides such as Takayasu's arteritis, giant cell arteritis, polyarteritis nodosa, and Behcet's disease have been associated with a subsequent aortic dissection. Marfan's syndrome is found in 5-9% of individuals who suffer from an aortic dissection. In this subset, the incidence in young individuals is increased. Individuals with Marfan syndrome tend to have aneurysms of the aorta and are more prone to proximal dissections of the aorta.

Turner syndrome also increases the risk of aortic dissection, by aortic root dilatation.

Chest trauma leading to aortic dissection can be divided into two groups based on cause: blunt chest trauma (commonly seen in car accidents) and iatrogenic. Iatrogenic causes include trauma during cardiac catheterization or due to an intra-aortic balloon pump.

Aortic dissection may be a late sequela of heart surgery. About 18% of individuals who present with an acute aortic dissection have a history of open-heart surgery. Individuals who have undergone aortic valve replacement for aortic insufficiency are at particularly high risk because aortic insufficiency causes increased blood flow in the ascending aorta. This can cause dilatation and weakening of the walls of the ascending aorta.

Syphilis only potentially causes aortic dissection in its tertiary stage.

Significant mitral valve regurgitation has a prevalence of approximately 2% of the population, affecting males and females equally. It is one of the two most common valvular heart diseases in the elderly.

Inheritance is thought to be rather complex. There is a good amount of evidence that shows the disease is autosomal 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. Still other studies show that mutations in smooth muscle cell-specific isoforms of alpha actin and beta myosin heavy chain may cause FAD. Mutations in the genes TGFBR 1 and 2 are known to cause dissections in aortas with normal diameter size (>4.3 cm) and gene "FPN1" mutations typically affect aortas with larger diameters (<4.4 cm).

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 aneurysm 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.

Establishing the incidence of aortic dissection has been difficult because many cases are only diagnosed after death (which may have been attributed to another cause), and is often initially misdiagnosed. Aortic dissection affects an estimated 2.0–3.5 people per every 100,000 every year. Studies from Sweden suggest that the incidence of aortic dissection may be rising. Men are more commonly affected than women: 65% of all people with aortic dissection are male. The mean age at diagnosis is 63 years. In females before the age of 40, half of all aortic dissections occur during pregnancy (typically in the third trimester or early postpartum period).

This type of aneurysm is typically congenital and may be associated with heart defects. It is sometimes associated with Marfan syndrome or Loeys–Dietz syndrome, but may also result from Ehlers–Danlos syndrome, bicuspid aortic valve, atherosclerosis, hypoplastic left heart syndrome, syphilis, cystic medial necrosis, chest injury, or infective endocarditis.

Sack–Barabas syndrome is rare and has an estimated prevalence of 1 in 100,000 to 200,000.

The initial clinical manifestation of vascular problems in patients with SBS is early, about 25% have their first symptoms at age 20 and more than 80% of patients have had at least one complication by the age of 40.

The median survival for one study of SBS patients was only 48 years.

Annuloaortic ectasia is a dilation of the proximal ascending aorta and aortic annulus. It may cause aortic regurgitation, thoracic aortic dissection, aneurysm and rupture. It is often associated with connective tissue diseases like Marfan syndrome and Ehlers Danlos Syndrome. It can also be a complication due to tertiary syphilis. In tertiary syphilis the aortic root becomes so dilated that the aortic valve becomes incompetent and cor bovinum results.

The term was first coined by the American heart surgeon Denton Cooley in 1961.

JLNS patients with "KCNQ1" mutations are particularly prone to pathological lengthening of the QT interval, which predisposes them to episodes of "torsades de pointes" and sudden cardiac death. In this context, if the patient has had syncopal episodes or history of cardiac arrest, an implantable cardiac defibrillator should be used in addition to a beta blocker such as propranolol.

Many factors influence the time course and extent of remodeling, including the severity of the injury, secondary events (recurrent ischemia or infarction), neurohormonal activation, genetic factors and gene expression, and treatment. Medications may attenuate remodeling. Angiotensin-converting enzyme (ACE) inhibitors have been consistently shown to decrease remodeling in animal models or transmural infarction and chronic pressure overload. Clinical trials have shown that ACE inhibitor therapy after myocardial infarction leads to improved myocardial performance, improved ejection fraction, and decreased mortality compared to patients treated with placebo. Likewise, inhibition of aldosterone, either directly or indirectly, leads to improvement in remodeling. Carvedilol, a 3rd generation beta blocker, may actually reverse the remodeling process by reducing left ventricular volumes and improving systolic function. Early correction of congenital heart defects, if appropriate, may prevent remodeling, as will treatment of chronic hypertension or valvular heart disease. Often, reverse remodeling, or improvement in left ventricular function, will also be seen.