The definitive treatment for Heyde's syndrome is surgical replacement of the aortic valve. Recently, it has been proposed that transcatheter aortic valve implantation (TAVI) can also be used for definitive management. Direct surgical treatment of the bleeding (e.g. surgical resection of the bleeding portion of the bowel) is only rarely effective.

Medical management of symptoms is possible also, although by necessity temporary, as definitive surgical management is required to bring levels of von Willebrand factor back to normal. In severe bleeding, blood transfusions and IV fluid infusions can be used to maintain blood pressure. In addition, desmopressin (DDAVP) is known to be effective in people with von Willebrand's disease, including people with valvular heart disease. Desmopressin stimulates release of von Willebrand factor from blood vessel endothelial cells by acting on the V2 receptor, which leads to decreased breakdown of Factor VIII. Desmopressin is thus sometimes used directly to treat mild to moderate acquired von Willebrand's disease and is an effective prophylactic agent for the reduction of bleeding during heart valve replacement surgery.

The exact prevalence of the syndrome is unknown, because both aortic stenosis and angiodysplasia are common diseases in the elderly. A retrospective chart review of 3.8 million people in Northern Ireland found that the incidence of gastrointestinal bleeding in people with any diagnosis of aortic stenosis (they did not subgroup people by severity) was just 0.9%. They also found that the reverse correlation—the incidence of aortic stenosis in people with gastrointestinal bleeding—was 1.5%. However, in 2003 a study of 50 people with aortic stenosis severe enough to warrant immediate valve replacement found GI bleeding in 21% of people, and another study done in the USA looking at angiodysplasia rather than GI bleeding found that the prevalence of aortic stenosis was 31% compared to 14% in the control group.

If the anemia is severe, blood transfusion is required before any other intervention is considered. Endoscopic treatment is an initial possibility, where cautery or argon plasma coagulation (APC) treatment is applied through the endoscope. Failing this, angiography and emolization with particles is another microinvasive treatment option, which avoids the need for surgery and bowel resection. Here, the vessel supplying the angiodysplasia is selectively catheterized and embolizaed with microparticles. Resection of the affected part of the bowel may be needed if the other modalities fail. However, the lesions may be widespread, making such treatment impractical.

If the bleeding is from multiple or inaccessible sites, systemic therapy with medication may be necessary. First-line options include the antifibrinolytics tranexamic acid or aminocaproic acid. Estrogens can be used to stop bleeding from angiodysplasia. Estrogens cause mild hypercoaguability of the blood. Estrogen side effects can be dangerous and unpleasant in both sexes. Changes in voice and breast swelling is bothersome in men, but older women often report improvement of libido and perimenopausal symptoms. (The worries about hormone replacement therapy/HRT, however, apply here as well.)

In difficult cases, there have been positive reports about octreotide and thalidomide.

In severe cases or cases not responsive to either endoscopic or medical treatment, surgery may be necessary to arrest the bleeding.

Acute decompensated heart failure due to AS may be temporarily managed by an intra-aortic balloon pump while pending surgery. In those with high blood pressure nitroprusside may be carefully used. Phenylephrine may be used in those with very low blood pressure.

If untreated, severe symptomatic aortic stenosis carries a poor prognosis with a 2-year mortality rate of 50-60% and a 3-year survival rate of less than 30%. Prognosis after aortic valve replacement for people who are younger than 65 is about five years less than that of the general population; for people older than 65 it is about the same.

As there is no known cure, Loeys–Dietz syndrome is a lifelong condition. Due to the high risk of death from aortic aneurysm rupture, patients should be followed closely to monitor aneurysm formation, which can then be corrected with interventional radiology or vascular surgery.

Previous research in laboratory mice has suggested that the angiotensin II receptor antagonist losartan, which appears to block TGF-beta activity, can slow or halt the formation of aortic aneurysms in Marfan syndrome. A large clinical trial sponsored by the National Institutes of Health is currently underway to explore the use of losartan to prevent aneurysms in Marfan syndrome patients. Both Marfan syndrome and Loeys–Dietz syndrome are associated with increased TGF-beta signaling in the vessel wall. Therefore, losartan also holds promise for the treatment of Loeys–Dietz syndrome. In those patients in which losartan is not halting the growth of the aorta, irbesartan has been shown to work and is currently also being studied and prescribed for some patients with this condition.

If an increased heart rate is present, atenolol is sometimes prescribed to reduce the heart rate to prevent any extra pressure on the tissue of the aorta. Likewise, strenuous physical activity is discouraged in patients, especially weight lifting and contact sports.

Histologically, it resembles telangiectasia and development is related to age and strain on the bowel wall. It is a degenerative lesion, acquired, probably resulting from chronic and intermittent contraction of the colon that is obstructing the venous drainage of the mucosa. As time goes by the veins become more and more tortuous, while the capillaries of the mucosa gradually dilate and precapillary sphincter becomes incompetent. Thus is formed an arteriovenous malformation characterized by a small tuft of dilated vessels.

Although angiodysplasia is probably quite common, the risk of bleeding is increased in disorders of coagulation. A classic association is Heyde's syndrome (coincidence of aortic valve stenosis and bleeding from angiodysplasia).

In this disorder, von Willebrand factor (vWF) is proteolysed due to high shear stress in the highly turbulent blood flow around the aortic valve. vWF is most active in vascular beds with high shear stress, including angiodysplasias, and deficiency of vWF increases the bleeding risk from such lesions.

Warkentin "et al." argue that apart from aortic valve stenosis, some other conditions that feature high shear stress might also increase the risk of bleeding from angiodysplasia.

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.

It can result in many abnormal heart rhythms (arrhythmias), including sinus arrest, sinus node exit block, sinus bradycardia, and other types of bradycardia (slow heart rate).

Sick sinus syndrome may also be associated with tachycardias (fast heart rate) such as atrial tachycardia (PAT) and atrial fibrillation. Tachycardias that occur with sick sinus syndrome are characterized by a long pause after the tachycardia. Sick sinus syndrome is also associated with azygos continuation of interrupted inferior vena cava.

Treatment for Romano–Ward syndrome can "deal with" the imbalance between the right and left sides of the sympathetic nervous system which may play a role in the cause of this syndrome. The imbalance can be temporarily abolished with a left stellate ganglion block, which shorten the QT interval. If this is successful, surgical ganglionectomy can be performed as a permanent treatment.Ventricular dysrhythmia may be managed by beta-adrenergic blockade (propranolol)

For patients with vWD type 1 and vWD type 2A, desmopressin is available as different preparations, recommended for use in cases of minor trauma, or in preparation for dental or minor surgical procedures. Desmopressin stimulates the release of vWF from the Weibel-Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII) three- to five-fold. Desmopressin is also available as a preparation for intranasal administration (Stimate) and as a preparation for intravenous administration. Recently, the FDA has approved the use of Baxalta’s Vonvendi. This is the first recombinant form of vWF. The effectiveness of this treatment is different than desmopressin because it only contains vWF, not vWF with the addition of FVIII. This treatment is only recommended for use by individuals who are 18 years of age or older.

Desmopressin is contraindicated in vWD type 2b because of the risk of aggravated thrombocytopenia and thrombotic complications. Desmopressin is probably not effective in vWD type 2M and is rarely effective in vWD type 2N. It is totally ineffective in vWD type 3.

For women with heavy menstrual bleeding, estrogen-containing oral contraceptive medications are effective in reducing the frequency and duration of the menstrual periods. Estrogen and progesterone compounds available for use in the correction of menorrhagia are ethinylestradiol and levonorgestrel (Levona, Nordette, Lutera, Trivora). Administration of ethinylestradiol diminishes the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, leading to stabilization of the endometrial surface of the uterus.

Desmopressin is a synthetic analog of the natural antidiuretic hormone vasopressin. Its overuse can lead to water retention and dilutional hyponatremia with consequent convulsion.

For patients with vWD scheduled for surgery and cases of vWD disease complicated by clinically significant hemorrhage, human-derived medium purity factor VIII concentrates, which also contain von Willebrand factors, are available for prophylaxis and treatment. Humate P, Alphanate, Wilate and Koate HP are commercially available for prophylaxis and treatment of vWD. Monoclonally purified factor VIII concentrates and recombinant factor VIII concentrates contain insignificant quantity of vWF, so are not clinically useful.

Development of alloantibodies occurs in 10-15% of patients receiving human-derived medium-purity factor VIII concentrates and the risk of allergic reactions including anaphylaxis must be considered when administering these preparations. Administration of the latter is also associated with increased risk of venous thromboembolic complications.

Blood transfusions are given as needed to correct anemia and hypotension secondary to hypovolemia. Infusion of platelet concentrates is recommended for correction of hemorrhage associated with platelet-type vWD.

The antifibrinolytic agents epsilon amino caproic acid and tranexamic acid are useful adjuncts in the management of vWD complicated by clinical hemorrhage. The use topical thrombin JMI and topical Tisseel VH are effective adjuncts for correction of hemorrhage from wounds.

Artificial pacemakers have been used in the treatment of sick sinus syndrome.

Bradyarrhythmias are well controlled with pacemakers, while tachyarrhythmias respond well to medical therapy.

However, because both bradyarrhythmias and tachyarrhythmias may be present, drugs to control tachyarrhythmia may exacerbate bradyarrhythmia. Therefore, a pacemaker is implanted before drug therapy is begun for the tachyarrhythmia.

Romano–Ward syndrome is the major variant of "long QT syndrome". It is a condition that causes a disruption of the heart's normal rhythm. This disorder is a form of long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats; if untreated, the irregular heartbeats can lead to fainting, seizures, or sudden death

Holt–Oram syndrome (also called Heart and Hand Syndrome, atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs) and may also cause heart problems. The syndrome includes an absent radial bone in the arms, an atrial septal defect, and a first degree heart block. Thalidomide syndrome can produce similar morphology to Holt–Oram syndrome, sufficient to be considered a phenocopy.

Von Willebrand disease can also affect some breeds of dogs, notably the Doberman Pinscher, and screening is offered for known breeds.

It is named for Mary Holt and Samuel Oram, who published a paper on it in 1960.

Individuals with LGL syndrome do not carry an increased risk of sudden death. The only morbidity associated with the syndrome is the occurrence of paroxysmal episodes of tachycardia which may be of several types, including sinus tachycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, or even ventricular tachycardia.

Surgery is typically used to correct structural heart defects and syndactyly. Propanolol or beta-adrenergic blockers are often prescribed as well as insertion of a pacemaker to maintain proper heart rhythm. With the characterization of Timothy syndrome mutations indicating that they cause defects in calcium currents, it has been suggested that calcium channel blockers may be effective as a therapeutic agent.

Harlequin syndrome is not debilitating so treatment is not normally necessary. In cases where the individual may feel socially embarrassed, contralateral sympathectomy may be considered, although compensatory flushing and sweating of other parts of the body may occur. In contralateral sympathectomy, the nerve bundles that cause the flushing in the face are interrupted. This procedure causes both sides of the face to no longer flush or sweat. Since symptoms of Harlequin syndrome do not typically impair a person’s daily life, this treatment is only recommended if a person is very uncomfortable with the flushing and sweating associated with the syndrome.

Heart-hand syndromes are a group of rare diseases that manifest with both heart and limb deformities.

, known heart-hand syndromes include Holt–Oram syndrome, Berk–Tabatznik syndrome, heart-hand syndrome type 3, brachydactyly-long thumb syndrome, patent ductus arteriosus-bicuspid aortic valve syndrome and heart hand syndrome, Slovenian type.

Heart-hand syndrome type 1 is more commonly known as Holt–Oram syndrome. Is the most prevalent form of heart-hand syndrome.

It is an autosomal dominant disorder that affects bones in the arms and hands (the upper limbs) and may also cause heart problems. The syndrome includes an absent radial bone in the arms, an atrial septal defect, and a first degree heart block.

The prognosis for patients diagnosed with Timothy syndrome is very poor. Of 17 children analyzed in one study, 10 died at an average age of 2.5 years. Of those that did survive, 3 were diagnosed with autism, one with an autism spectrum disorder, and the last had severe delays in language development. One patient with atypical Timothy syndrome was largely normal with the exception of heart arrhythmia. Likewise, the mother of two Timothy syndrome patients also carried the mutation but lacked any obvious phenotype. In both of these cases, however, the lack of severity of the disorder was due to mosaicism.

In August 2016, researchers at the Instituto de Assistência dos Servidores do Estado do Rio de Janeiro used botulinum toxin as a method to block the acetylcholine release from the presynaptic neurons. Although they have seen a reduction in one sided flushing, sweating still occurs.

There have been case studies of individuals whom have experienced this syndrome after an operation. Two patients, a 37-year-old and 58-year-old female patients suffering from metastatic cancer were scheduled for placement of an intrathecal pump drug delivery system. After the intrathecal pump was placed, certain medications were given to the patients. Once the medications were administered, both patients had one sided facial flushes, closely resembling Harlequin Syndrome. Patients were given neurological exams to confirm that their nerves were still intact. An MRI was performed and showed no significant evidence of bleeding or nerve compression. After close observation for 16 hours, symptoms of the Harlequin syndrome was diminished and both patients did not have another episode.

Another case study was based on a 6-year-old male visiting an outpatient setting for one sided flushes during or after physical activity or exposed to heat. Vitals, laboratory tests, and CT scans were normal. Along with the flushes, the right pupil was 1.5 mm in size, while the left pupil was 2.5 mm in size; however, no ptosis, miosis, or enophthalmos was noted. The patient also had an MRI scan to rule out any lesion near the brain or spinal cord. No abnormalities were noted and the patient did not receive any treatments. The patient was diagnosed with idiopathic Harlequin syndrome.

Although the mechanism is still unclear, the pathophysiology of this condition, close monitoring, and reassurance are vital factors for successful management.

Lown–Ganong–Levine syndrome (LGL) is a pre-excitation syndrome of the heart due to abnormal electrical communication between the atria and the ventricles. Once thought to involve an accessory conduction pathway, it is grouped with Wolff–Parkinson–White syndrome as an atrioventricular re-entrant tachycardia (AVRT). Individuals with LGL syndrome have a short PR interval with normal QRS complexes and paroxysms of clinically-significant tachycardia. The syndrome is named after Bernard Lown, William Francis Ganong, Jr., and Samuel A. Levine.

Individuals with a short PR interval found incidentally on EKG were once thought to have LGL syndrome. However, subsequent studies have shown that a short PR interval in the absence of symptomatic tachycardia is simply a benign EKG variant.

After the first discovery and description of Marshall–Smith syndrome in 1971, research to this rare syndrome has been carried out.

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- Hoyme HE and Bull MJ: The Marshall-Smith Syndrome: Natural history beyond infancy. Western Society for Pediatric Research, Carmel, California, February, 1987. Clin Res 35:68A, 1987.

- Hoyme HE and Bull MJ: The Marshall-Smith Syndrome: Natural history beyond infancy. David W. Smith Morphogenesis and Malformations Workshop. Greenville, SC, August, 1987. Proceedings of the Greenwood Genetics Center 7:152, 1988.

- Hoyme HE, Byers PH, Guttmacher AE: Marshall–Smith syndrome: Further evidence of an osteochondrodysplasia in long-term survivors. David W. Smith Morphogenesis and Malformations Workshop, Winston-Salem, NC, August, 1992. Proceedings of the Greenwood Genetic Center 12:70, 1993.

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- Tzu-Jou Wang (2002). Marshall–Smith syndrome in a Taiwanese patient with T-cell immunodeficiency. Am J Med Genet Part A;112 (1):107-108.