Hypertrophic cardiomyopathy Totally Explained

Everything about Hypertrophic Cardiomyopathy totally explained

Hypertrophic cardiomyopathy, or HCM, is a disease of the myocardium (the muscle of the heart) in which a portion of the myocardium is hypertrophied (thickened) without any obvious cause. Though perhaps most famous as a leading cause of sudden cardiac death in young athletes
   HCM's more important significance is as a cause of sudden unexpected cardiac death in any age group and as a cause of disabling cardiac symptoms.
   A cardiomyopathy is any disease that primarily affects the muscle of the heart. In HCM, the normal alignment of muscle cells is disrupted, a phenomenon known as myocardial disarray. HCM also causes disruptions of the electrical functions of the heart. HCM is believed to be due to a mutation in one of many genes that results in a mutated myosin heavy chain, one of the components of the myocyte (the muscle cell of the heart). Depending on whether the distortion of normal heart anatomy causes an obstruction of the outflow of blood from the left ventricle of the heart, HCM can be defined as obstructive or non-obstructive. The obstructive variant of HCM, Hypertrophic obstructive cardiomyopathy (HOCM) has also historically been known as idiopathic hypertrophic subaortic stenosis (IHSS) and asymmetric septal hypertrophy (ASH). Another, non-obstructive variant of HCM is apical hypertrophic cardiomyopathy , first described in individuals of Japanese descent).
   While most literature so far focuses on European, American, and Japanese populations, HCM appears in all racial groups. The incidence of HCM is about 0.2% to 0.5% of the general population.

Genetics

Hypertrophic cardiomyopathy is inherited as an autosomal dominant trait and is attributed to mutations in one of a number of genes that encode for one of the sarcomere proteins including beta-cardiac myosin heavy chain (the first gene identified), cardiac actin, cardiac troponin T, alpha-tropomyosin, cardiac troponin I, cardiac myosin-binding protein C, and the myosin light chains. Currently there are more than 400 mutations in these genes. Approximately 45% of these mutations occur in the β myosin heavy chain gene on chromosome 14 q11.2-3, while approximately 35% involve the cardiac myosin binding protein C gene. The prognosis is variable, based on the gene mutation. In individuals without a family history of HCM, the most common cause of the disease is a de novo mutation of the gene that produces the β-myosin heavy chain.
An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. 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
.

Anatomic characteristics

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 two-thirds of individuals with HCM have asymmetric septal hypertrophy.
About 25% of individuals with HCM demonstrate an obstruction to the outflow of blood from the left ventricle during rest. In other individuals obstruction only occurs under certain conditions. This is known as dynamic outflow obstruction, because the degree of obstruction is variable and is dependent on the amount of blood in the ventricle immediately before ventricle systole (contraction).

Dynamic outflow obstruction

Dynamic outflow obstruction (when present in HCM) is usually due to systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. Systolic anterior motion of the mitral valve (SAM) was initially thought to be due to the septal subaortic bulge, narrowing the outflow tract, causing high velocity flow and a Venturi effect — a local underpressure in the outflow tract. Low pressure was thought to suck the mitral valve anteriorly into the septum. But SAM onset is observed to be a low velocity phenomenon: SAM begins at velocities no different from those measured in normals
   . Hence, the magnitude and importance of Venturi forces in the outflow tract are much less than previously thought, and Venturi forces can't be the main force that initiates SAM.
   Recent echocardiographic evidence indicates that drag, the pushing force of flow is the dominant hydrodynamic force on the mitral leaflets
   . In obstructive HCM the mitral leaflets are often large
   and are anteriorly positioned in the LV cavity
   due to anteriorly positioned papillary muscles. As SAM progresses in early systole the angle between outflow and the protruding mitral leaflet increases. A greater surface area of the leaflets is now exposed to drag which amplifies the force on the leaflets – drag increases with increasing angle relative to flow Often, symptoms mimic those of congestive heart failure (esp. activity intolerance & dyspnea), but it must be noted that treatment is very different. To treat with diuretics (a mainstay of CHF treatment) will exacerbate symptoms in hypertrophic cardiomyopathy by decreasing ventricular volume and increasing outflow resistance.
   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, ventricular septal wall thickness over 3cm, hypotensive response to exercise, syncope (especially in children), and bradyarrhythmias (slow rhythms of the heart).

Physical examination

Differentiating hypertrophic cardiomyopathy and valvular aortic stenosis>

	Aortic stenosis	Hypertrophic cardiomyopathy
Echocardiography
Aortic valve calcification	Common	No
Dilated ascending aorta	Common	Rare
Ventricular hypertrophy	Concentric LVH	Asymmetric, often involving the septum
Physical examination
Murmur of AI	Common	No
Pulse pressure after PVC	Increased	Decreased
Valsalva maneuver	Decreased intensity of murmur	Increased intensity of murmur
Carotid pulsation	Normal or tardus et parvus	Brisk, jerky, or bisferiens pulse (a collapse of the pulse followed by a secondary rise)

The physical findings of HCM are associated with the dynamic outflow obstruction that's 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).
If dynamic outflow obstruction exists, physical examination findings that can be elicited include the pulsus bisferiens and the double apical impulse with each ventricular contraction. These findings, when present, can help differentiate HCM from aortic stenosis. In addition, if the individual has premature ventricular contractions (PVCs), the change in the carotid pulse intensity in the beat after the PVC can help differentiate HCM from aortic stenosis. In individuals with HCM, the pulse pressure will decrease in the beat after the PVC, while in aortic stenosis, the pulse pressure will increase.

Diagnostic testing

A diagnosis of hypertrophic cardiomyopathy is based upon a number of features of the disease process. While there's use of echocardiography, cardiac catheterization, or cardiac MRI in the diagnosis of the disease, other important factors include ECG findings and if there's any family history of HCM or unexplained sudden death in otherwise healthy individuals.

Cardiac catheterization

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.

Treatment

In all patients with hypertrophic cardiomyopathy risk stratification is essential to attempt to ascertain which patients are at risk for sudden cardiac death. Alternately a calcium channel blocker such as verapamil may be substituted for beta-blockade. It should be stressed that most patients' symptoms may be managed medically without needing to resort to inteventions such as surgical septal myectomy, alcohol septal ablation or pacing. Severe symptoms in non-obstructive HCM may actually be more difficult to treat because there's no obvious target (obstruction) to treat. Medical therapy with verapamil and beta-blockade may improve symptoms. Diuretics should be avoided, as they reduce the intravascular volume of blood, decreasing the amount of blood available to distend the left ventricular outflow tract, leading to an increase in the obstruction to the outflow of blood in the left ventricle.

Surgical myectomy

Surgical septal myectomy is an open heart operation done to relieve symptoms in patients who remain severely symptomatic despite medical therapy. It has been performed successfully for more than 25 years. Surgical septal myectomy uniformly decreases left ventricular outflow tract obstruction and improves symptoms, and in experienced centers has a surgical mortality of 1%. It involves a midline thoracotomy (general anesthesia, opening the chest, and cardiopulmonary bypass) and removing a portion of the interventricular septum. With this in mind, a modification of the Morrow myectomy termed extended myectomy, mobilization and partial excision of the papillary muscles has become the excision of choice. In selected patients with particularly large redundant mitral valves, anterior leaflet plication may be added to complete separation of the mitral valve and outflow.

Alcohol septal ablation

Alcohol septal ablation, introduced by Ulrich Sigwart in 1994, is a percutaneous technique that involves injection of alcohol into one or more septal branches of the left anterior descending artery. This is a technique with results similar to the surgical septal myectomy procedure but is less invasive, since it doesn't involve general anaesthesia and opening of the chest wall and pericardium (which are done in a septal myomectomy). In a select population with symptoms secondary to a high outflow tract gradient, alcohol septal ablation can reduce the symptoms of HCM. In addition, older individuals and those with other medical problems, for whom surgical myectomy would pose increased procedural risk, would likely benefit from the lesser invasive septal ablation procedure.
When performed properly, an alcohol septal ablation induces a controlled heart attack, in which the portion of the interventricular septum that involves the left ventricular outflow tract is infarcted and will contract into a scar. Which patients are best served by surgical myectomy, alcohol septal ablation, or medical therapy is an important topic and one which is intensely debated in medical scientific circles.

Ventricular pacing

The use of a pacemaker has been advocated in a subset of individuals, in order to cause asynchronous contraction of the left ventricle. Since the pacemaker activates the interventricular septum before the left ventricular free wall, the gradient across the left ventricular outflow tract may decrease. This form of treatment has been shown to provide less relief of symptoms and less of a reduction in the left ventricular outflow tract gradient when compared to surgical myectomy.

Cardiac transplantation

In cases that are refractory to all other forms of treatment, cardiac transplantation is an option.

Related disorders

Feline hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats; the disease process and genetics are believed to be similar to the disease in humans. In Maine Coon and American Shorthair cat breeds, HCM has been confirmed as an autosomal dominant inherited trait. The first genetic mutation (in cardiac myosin binding protein C) responsible for feline hypertrophic cardiomyopathy was discovered in 2005 in Maine Coon cats. A test for this mutation is available. About one third of Maine Coon cats tested for the mutation have been shown to be either heterozygous or homozygous for the mutation, although many of these cats have no clinical signs of the disease. Some Maine Coon cats with clinical evidence of hypertrophic cardiomyopathy test negative for this mutation, strongly suggesting that a second mutation exists in the breed. The cardiac myosin binding protein C mutation hasn't been found in any other breed of cat with HCM.
While there's no cure for HCM, early detection, regular echocardiograms, and daily medicine (for example, Atenolol, Lotensin, Plavix) is key to prolonging an affected cat's life. Early signs may include a murmur or even heart failure. Unfortunately, death may occur without any other signs present, making the disease a difficult and often deadly one.

HCM in popular culture

In the CW television show One Tree Hill, characters Dan and Lucas Scott have HCM. Vivian Johnson on Without a Trace also has HCM.
   On the TV series Scrubs, in the first episode involving Jordan, Dr Kelso tells JD to run tests to check her for HCM.
   One of the players in Glory Road was benched with HCM.
   The main character of the 1997 film The Sixth Man, Antoine Taylor, played by actor Kadeem Hardison, died from HCM.
   In the Australian TV series Love My Way, Frankie and Charlie's daughter, Lou, dies suddenly from HCM.
   Miklós "Miki" Fehér a Hungarian football player died during a match with his team SL Benfica against Vitória Guimarães, on January 25, 2004.
   Marc-Vivien Foé is believed to have died due to hypertrophic cardiomyopathy.

Further Information

Get more info on 'Hypertrophic Cardiomyopathy'.

External Link Exchanges

Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:

<a href="http://hypertrophic_cardiomyopathy.totallyexplained.com">Hypertrophic cardiomyopathy Totally Explained</a>

Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned.