What causes hypertrophic cardiomyopathy?
Hypertrophic cardiomyopathy is attributed to mutation in one of a number of genes that encode for one of the sarcomere proteins (usually effecting either the α or β myosin heavy chain on chromosome 14 q11.2-3). While the severity of the disease process is dependant on the particular gene mutation, about 80% of cases are inherited in an autosomal dominant pattern. Other gene mutations that are associated with HCM include mutations in α-tropomyosin (on chromosome 15),
troponin T (on chromosome 1), and myosin-binding protein C (on chromosome 11). The prognosis is variable, based on the gene mutation.
The MYH7 gene (encoding the Β-myosin heavy chain) was the first specific gene identified in familial hypertrophic cardiomyopathy. About 50 percent of all familial cases involve mutation in the MYH7 gene. In individuals without a family history of HCM, the most common cause of the disease is also mutations of the gene that produces the β-myosin heavy chain. Many different mutations in this gene have been identified, and the prognosis is dependant on the particular mutation. An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) has been associated with some cases of HCM. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes.
Individuals with HCM have some degree of left ventricular hypertrophy. Usually this is an asymmetric hypertrophy, involving the inter-ventricular septum, and is known as asymmetric septal hypertrophy (ASH). This is in contrast to the concentric hypertrophy seen in aortic stenosis or hypertension. About 2/3 of individuals with HCM have asymmetric septal hypertrophy. Symptoms of HCM include shortness of breath, chest pain (sometimes known as angina), uncomfortable awareness of the heart beat (palpitation), light-headedness, dizziness, blackouts and sudden cardiac death. Risk factors for sudden death in individuals with HCM include a young age at first diagnosis (age < 30 years), an episode of aborted sudden death, a family history of HCM with sudden death of relatives, specific mutations in the genes encoding for troponin T and myosin, sustained supraventricular or ventricular tachycardia, recurrent syncope, and bradyarrhythmias (slow rhythms of the heart).
The physical findings of HCM are associated with the dynamic outflow obstruction that is often present with this disease. Upon auscultation, the cardiac murmur will sound similar to the murmur of aortic stenosis. However, this murmur will increase in intensity with any maneuver that decreases the volume of blood in the left ventricle (such as standing or the strain phase of a Valsalva maneuver). Upon cardiac catheterization, catheters can be placed in the left ventricle and the ascending aorta, to measure the pressure difference between these structures. In normal individuals, during ventricular systole, the pressure in the ascending aorta and the left ventricle will equalize, and the aortic valve is open. In individuals with aortic stenosis or with HCM with an outflow tract gradient, there will be a pressure gradient (difference) between the left ventricle and the aorta, with the left ventricular pressure higher than the aortic pressure. This gradient represents the degree of obstruction that has to be overcome in order to eject blood from the left ventricle.
The Brockenbrough-Braunwald-Morrow sign is observed in individuals with HCM with outflow tract gradient. This sign can be used to differentiate HCM from aortic stenosis. In individuals with aortic stenosis, after a premature ventricular contraction (PVC), the following ventricular contraction will be more forceful, and the pressure generated in the left ventricle will be higher. Because of the fixed obstruction that the stenotic aortic valve represents, the post-PVC ascending aortic pressure will increase as well. In individuals with HCM, however, the degree of obstruction will increase more than the force of contraction will increase in the post-PVC beat. The result of this is that the left ventricular pressure increases and the ascending aortic pressure decreases, with an increase in the LVOT gradient. While the Brockenbrough-Braunwald-Morrow sign is most dramatically demonstrated using simultaneous intra-cardiac and intra-aortic catheters, it can be seen on routine physical examination as a decrease in the pulse pressure in the post-PVC beat in individuals with HCM.
More information on cardiomyopathy
What is cardiomyopathy? - Cardiomyopathy is an alteration in the function of the heart muscle. Cardiomyopathy is the deterioration of the cardiac muscle of the heart wall.
What're the symptoms of cardiomyopathy? - The symptoms of cardiomyopathy include fatigue, shortness of breath, fainting, leg swelling, and an enlarged and tender liver.
How is cardiomyopathy diagnosed? - Cardiomyopathy can be diagnosed by characteristic physical findings, electrocardiogram, echocardiogram, cardiac catheterization and radionuclide angiography.
What is dilated cardiomyopathy? - Dilated cardiomyopathy (DCM) is the commonest form of cardiomyopathy, and one of the leading indications for heart transplantation.
What causes dilated cardiomyopathy? - No exact cause can be found for cardiomyopathy. Up to 30% of cases of dilated cardiomyopathy can be linked to heavy drinking.
What're the symptoms of dilated cardiomyopathy? - Typical signs and symptoms of dilated cardiomyopathy include fatigue, weakness, shortness of breath, and swelling of the legs and feet.
What're the treatments for dilated cardiomyopathy? - Treatment for dilated cardiomyopathy is focused on relieving the symptoms and the extra load on the heart. Lifestyle changes, medicines, and surgery may be needed.
What is hypertrophic cardiomyopathy? - Hypertrophic cardiomyopathy (HCM) is the second most common type of cardiomyopathy and results in excessive thickening of the heart walls.
What causes hypertrophic cardiomyopathy? - Hypertrophic cardiomyopathy is caused by the mutation in one of a number of genes that encode for one of the sarcomere proteins.
What're the symptoms of hypertrophic cardiomyopathy? - Symptoms of hypertrophic cardiomyopathy include shortness of breath, chest pain (angina), palpitations, dizziness and fainting attacks.
What's the treatment for hypertrophic cardiomyopathy? - Treatment of hypertrophic cardiomyopathy is directed towards decreasing the left ventricular outflow tract gradient and to abort arrhythmias.
What's arrhythmogenic right ventricular dysplasia? - Arrhythmogenic right ventricular dysplasia (ARVD) is a type of nonischemic cardiomyopathy that involves primarily the right ventricle.
What causes arrhythmogenic right ventricular dysplasia? - The cause of arrhythmogenic right ventricular dysplasia is largely unknown. Apoptosis appears to play a large role.
What's the treatment for arrhythmogenic right ventricular dysplasia? - Pharmacologic treatment of arrhythmogenic right ventricular dysplasia involves arrhythmia suppression and prevention of thrombus formation.
What is restrictive cardiomyopathy? - Restrictive cardiomyopathy (RCM) is the least common cardiomyopathy. Restrictive cardiomyopathy can be caused by a number of diseases.
How restrictive cardiomyopathy is diagnosed? - The diagnosis of restrictive cardiomyopathy is usually based on a physical examination, echocardiography, and other tests as needed.
What's the treatment for restrictive cardiomyopathy? - There is no effective treatment for restrictive cardiomyopathy. Treatment of a causative disease may reduce or stop the damage to the heart.
How is cardiomyopathy treated? - Beta-blocker medicines, and calcium antagonist medicines are the mainstay of treatment for cardiomyopathy. Surgery may be indicated for hypertrophic cardiomyopathy.