Hypertrophic cardiomyopathy
Encyclopedia
Hypertrophic cardiomyopathy 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. It is perhaps most well known as a leading cause of sudden cardiac death
in young athletes.
The occurrence of hypertrophic cardiomyopathy is a significant cause of sudden unexpected cardiac death in any age group and as a cause of disabling cardiac symptoms. Younger people are likely to have a more severe form of hypertrophic cardiomyopathy
HCM is frequently asymptomatic until sudden cardiac death, and for this reason some suggest routinely screening certain populations for this disease.
A cardiomyopathy
is a primary disease that affects the muscle of the heart. With hypertrophic cardiomyopathy (HCM), the sarcomeres (contractile elements) in the heart replicate causing heart muscle cells to increase in size, which results in the thickening of the heart muscle. In addition, 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 most commonly due to a mutation in one of 9 sarcomeric gene
s that results in a mutated protein in the sarcomere, the primary component of the myocyte
(the muscle cell of the heart).
While most literature so far focuses on European, American, and Japanese populations, HCM appears in all racial groups. The prevalence of HCM is about 0.2% to 0.5% of the general population.
Myosin
heavy chain mutations are associated with development of familial hypertrophic cardiomyopathy.
from the left ventricle
of the heart, HCM can be defined as obstructive or non-obstructive.
protein
s including:
About 50-60% of patients with a high index of clinical suspicion for HCM will have a mutation identified in at least 1 of 9 sarcomeric 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. Since HCM is typically an autosomal dominant trait, children of an HCM parent have 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified through genetic testing, family-specific genetic testing can be used to identify relatives at-risk for the disease (HCM Genetic Testing Overview). 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
.
Once HCM has been identified in a family, immediate testing of all family members will help to identify those at risk. Children often do not show signs of HCM; the first sign many children display is sudden cardiac arrest. Both invasive and non-invasive techniques exist to detect thickening of the left ventricle and other abnormalities associated with HCM. The most common non-invasive diagnostic test for detecting HCM is electrocardiography, though the most sensitive test for diagnosing HCM is genetic testing.
Beta blockers are often prescribed as the first medical treatment for HCM in children. Many options exist, so it is important to remember to inform one's doctor if undesirable side-effects occur so a switch can be made. Stopping a beta blocker treatment without the consent of your doctor is never advised.
. 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).
. 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 cannot 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 that at surgery are often "agglutinated" onto the LV anterior wall by abnormal attachments
.
The mid-septal bulge aggravates the malposition of the valve and redirects outflow so that it comes from a lateral and posterior direction. The abnormally directed outflow may be visualized behind and lateral to the enlarged mitral valve, where it catches it, and pushes it into the septum
.
There is a crucial overlap between the inflow and outflow portions of the left ventricle
.
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. An analogy is an open door in a drafty corridor: the door starts by moving slowly and then accelerates as it presents a greater surface area to the wind and finally it slams shut. The necessary conditions that predispose to SAM are: anterior position of the mitral valve in the LV, altered LV geometry that allows flow to strike the mitral valve from behind, and chordal slack
.
SAM may considered anteriorly directed mitral prolapse
.
In both conditions the mitral valve is enlarged and is displaced in systole by the pushing force of flow resulting in mitral regurgitation.
Because the mitral valve leaflet doesn't get pulled into the left ventricular outflow tract (LVOT) until after the aortic valve opens, the initial upstroke of the arterial pulse will be normal. When the mitral valve leaflet gets pushed into the LVOT, the arterial pulse will momentarily collapse and be followed by a second rise, as the left ventricular pressure overcomes the increased obstruction that SAM of the mitral valve causes. This can be seen on the physical examination as a double tap upon palpation of the apical impulse and as a double pulsation upon palpation of the carotid pulse, known as bifid pulse.
s of HCM include dyspnea (shortness of breath), chest pain (sometimes known as angina), uncomfortable awareness of the heart beat
(palpitations), lightheadedness
, fatigue, fainting (called syncope
) and sudden cardiac death
. Dyspnea
is largely due to increased stiffness of the left ventricle, which impairs filling of the ventricles and leads to elevated pressure in the left ventricle and left atrium. Symptoms are not closely related to the presence or severity of an outflow tract gradient. Often, symptoms mimic those of congestive heart failure
(esp. activity intolerance & dyspnea), but 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
, ventricular septal wall thickness over 3 cm, hypotensive response to exercise, recurrent syncope
(especially in children), 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, a murmur due to HCM 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
). Classically, the murmur is also loudest at the left parasternal edge, 4th intercostal space, rather than in the aortic area.
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 contraction
s (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. However, the murmur intensity increases with both Aortic Stenosis and HCM post-PVC.
, and is the leading cause of sudden cardiac death in young athletes. HCM can be detected with an echocardiogram with 80%+ accuracy, which can be preceded by screening with an electrocardiogram
(ECG) to test for heart abnormalities. History and physical examination alone are ineffective, giving warning of heart abnormalities in only 3% of patients before sudden cardiac death. One study found that the incidence of sudden cardiovascular death in young competitive athletes declined in the Veneto region of Italy by 89% since introduction of routine Hypertrophic Cardiomyopathy Screening
of athletes.
In the United States such screening is not routine and the American Heart Association
has "consistently opposed" routine screening.
of hypertrophic cardiomyopathy is based upon a number of features of the disease process. While there is use of echocardiography, cardiac catheterization
, or cardiac MRI in the diagnosis of the disease, other important factors include ECG
and genetic test findings and if there is any family history of HCM or unexplained sudden death in otherwise healthy individuals.
Upon cardiac catheterization
, catheter
s 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.
, atenolol, bisoprolol
, propranolol). If symptoms and gradient persist, disopyramide
may be added to the beta-blocker.
Alternately a calcium channel blocker such as verapamil
may be substituted for a beta blocker. It should be stressed that most patients' symptoms may be managed medically without needing to resort to interventions 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 is 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.
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 less than 1%. It involves a median sternotomy (general anesthesia, opening the chest, and cardiopulmonary bypass) and removing a portion of the interventricular septum. Surgical myectomy resection focused just on the subaortic septum, to increase the size of the outflow tract to reduce Venturi forces may be inadequate to abolish systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. With this limited sort of resection the residual mid-septal bulge still redirects flow posteriorly: SAM persists because flow still gets behind the mitral valve. It is only when the deeper portion of the septal bulge is resected that flow is redirected anteriorly away from the mitral valve, abolishing SAM.
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.
, 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 does not 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.
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.
in cat
s; the disease process and genetics are believed to be similar to the disease in human
s. 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 identified in Maine Coon cats has not been found in any other breed of cat with HCM but more recently another myosin binding protein C mutation has been identified in Ragdoll cats with HCM.
Turkish Angoras also may be susceptible to HCM because of this gene. The CatScan study performed at the Royal Veterinary College
, London, is looking at the prevalence of the disease within a normal population of apparently healthy domestic cats (non-pedigree). This study has just begun (October 2009) and the results of should be available in early 2012.
While there is no cure for HCM, early detection and regular echocardiograms are key to trying to ward off life-threatening problems. 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. While medication is commonly given to cats with HCM that have no clinical signs, no medication has been shown to be helpful at this stage and it has been shown that an ACE inhibitor is not beneficial until heart failure is present (at which time a diuretic is most beneficial). Diltiazem generally produces no demonstrable benefit. Atenolol is commonly administered when systolic anterior motion of the mitral valve is present.
Thromboembolic disease (TED) is relatively common sequelae of Feline HCM. The aetiology remains a little uncertain, but it is thought that ischemic damage to the hypertrophied left ventricular myocardium facilitates thrombus formation and subsequent embolism. Classically the embolus lodges at the iliac bifurcation of the aorta, occluding either one or both of the common iliac arteries. Clinically this presents as a cat with complete loss of function in one or both hindlimbs. The hindlimbs are cold, and the cat is in considerable pain. This pain derives from the exaggerated inflammatory response to the embolus at the point of impact, and the inflammatory mediators released generally have a vasoconstrictor effect further exacerbating the problem. Emboli may, rarely, lodge in other locations, typically the renal or ovarian/testicular arteries as they exit the abdominal aorta.
Treatment of TED is variable - typically very low doses of aspirin may be prescribed (aspirin however is extremely toxic to cats and should only be prescribed and administered by a veterinary surgeon). Plavix is also another widely used drug that may or may not prevent clot formation in HCM cats. The FATCAT study at Purdue University is addressing the efficacy of aspirin vs. Plavix for the prevention of a second clot in cats that have already experienced a clot. Thrombolytic agents (e.g., tissue plasminogen activators) have been used successfully, but their cost is usually prohibitively high in veterinary medicine. Despite the relative efficacy of treatment, the prognosis for cats with TED is poor as they are likely to have significant HCM already, and a recurrent bout of TED is very likely. For this reason euthanasia is often considered in TED cats.
of Cameroon during a 2003 FIFA Confederations Cup
match, his autopsy revealed hypertrophic cardiomyopathy. Miklós "Miki" Fehér
, a Hungarian football player who died during a match on January 25, 2004, also suffered from HCM.
Other noted athletes believed or suspected to have died from HCM include NFL
players Thomas Herrion
, Mitch Frerotte
, Damien Nash
, Gaines Adams
, and Derrick Faison; NBA
players Reggie Lewis
, Jason Collier
, and Kevin Duckworth
; NHL
player Sergei Zholtok
; baseball
pitcher Joe Kennedy; long distance runner Ryan Shay
; Loyola Marymount basketball star Hank Gathers
; Loyola Marymount soccer player David Kucera; NFL Defensive End Kansas State
football player Anthony Bates; OHL
Windsor Spitfires
captain Mickey Renaud; and Russian ice hockey
star Alexei Cherepanov
. Jesse Marunde
, an American strongman
, died of HCM in 2007 after a workout at his gym.
On December 10, 2008, NBA player Cuttino Mobley
announced his retirement due to worsening HCM. The disease also ended the career of former Wake Forest
star Robert O'Kelley, after a mandatory EKG in Brazil discovered his condition in 2006.
British comedy actor Leonard Rossiter
died from hypertrophic cardiomyopathy in 1984 while waiting to go onstage at the Lyric Theatre, London. The autopsy of actor Corey Haim
identified HCM as one of the contributing causes (along with pneumonia
and coronary arteriosclerosis
) for his death in 2010. American pornographic actress Aurora Jolie also has HCM.
television show One Tree Hill
, characters Dan and Lucas Scott
have HCM.
In the Fox
series Beverly Hills 90210, Joe Bradley, a quarterback for California University and boyfriend of Donna Martin for much of season 6, is diagnosed with HCM by Donna's father, Dr. John Martin.
Vivian Johnson
on Without a Trace
also has HCM.
Willie Cager 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.
In an episode of Eli Stone
(10/21/2008) the character Grace Fuller played by Katie Holmes
has HCM.
The lead girl in the Korean Movie A Millionaire's First Love
played by Lee Yeon Hee died from HCM.
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
of the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
) in which a portion of the myocardium is hypertrophied
Left ventricular hypertrophy
Left ventricular hypertrophy is the thickening of the myocardium of the left ventricle of the heart.-Causes:While ventricular hypertrophy occurs naturally as a reaction to aerobic exercise and strength training, it is most frequently referred to as a pathological reaction to cardiovascular...
(thickened) without any obvious cause. It is perhaps most well known as a leading cause of sudden cardiac death
Sudden Cardiac Death
Sudden cardiac death is natural death from cardiac causes, heralded by abrupt loss of consciousness within one hour of the onset of acute symptoms. Other forms of sudden death may be noncardiac in origin...
in young athletes.
The occurrence of hypertrophic cardiomyopathy is a significant cause of sudden unexpected cardiac death in any age group and as a cause of disabling cardiac symptoms. Younger people are likely to have a more severe form of hypertrophic cardiomyopathy
HCM is frequently asymptomatic until sudden cardiac death, and for this reason some suggest routinely screening certain populations for this disease.
A cardiomyopathy
Cardiomyopathy
Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...
is a primary disease that affects the muscle of the heart. With hypertrophic cardiomyopathy (HCM), the sarcomeres (contractile elements) in the heart replicate causing heart muscle cells to increase in size, which results in the thickening of the heart muscle. In addition, the normal alignment of muscle cells is disrupted, a phenomenon known as myocardial disarray
Myocardial disarray
Myocardial disarray, also known as myocyte disarray, is a term to describe the loss of the normal parallel alignment of myocytes . Instead, the myocytes usually form circles around foci of connective tissue...
. HCM also causes disruptions of the electrical functions of the heart. HCM is most commonly due to a mutation in one of 9 sarcomeric gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s that results in a mutated protein in the sarcomere, the primary component of the myocyte
Myocyte
A myocyte is the type of cell found in muscles. They arise from myoblasts.Each myocyte contains myofibrils, which are long, long chains of sarcomeres, the contractile units of the cell....
(the muscle cell of the heart).
While most literature so far focuses on European, American, and Japanese populations, HCM appears in all racial groups. The prevalence of HCM is about 0.2% to 0.5% of the general population.
Myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
heavy chain mutations are associated with development of familial hypertrophic cardiomyopathy.
Obstructive and non-obstructive
Depending on whether the distortion of normal heart anatomy causes an obstruction of the outflow of bloodBlood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
from the left ventricle
Left ventricle
The left ventricle is one of four chambers in the human heart. It receives oxygenated blood from the left atrium via the mitral valve, and pumps it into the aorta via the aortic valve.-Shape:...
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 idiopathicIdiopathicIdiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
hypertrophic subaortic stenosis (IHSS) and asymmetric septal hypertrophy (ASH).
- Another, non-obstructive variant of HCM is apical hypertrophic cardiomyopathy, also called Yamaguchi Syndrome or Yamaguchi Hypertrophy, first described in individuals of JapanJapanJapan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
ese descent.
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 sarcomereSarcomere
A sarcomere is the basic unit of a muscle. Muscles are composed of tubular muscle cells . Muscle cells are composed of tubular myofibrils. Myofibrils are composed of repeating sections of sarcomeres, which appear under the microscope as dark and light bands...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s including:
| Gene | Locus | Type |
|---|---|---|
| MYH7 MYH7 MYH7 is a gene encoding a myosin heavy chain beta isoform expressed primarily in the heart.Changes in the relative abundance of MHC-β and MHC-α correlate with the contractile velocity of cardiac muscle... |
14q12 | CMH1 |
| TNNT2 TNNT2 Troponin T type 2 , also known as TNNT2, is a protein which in humans is encoded by the TNNT2 gene.The protein encoded by this gene is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to... |
1q32 | CMH2 |
| TPM1 TPM1 Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene.-Further reading:- External links :*... |
15q22.1 | CMH3 |
| MYBPC3 | 11p11.2 | CMH4 |
| ? | ? | CMH5 |
| PRKAG2 PRKAG2 5'-AMP-activated protein kinase subunit gamma-2 is an enzyme that in humans is encoded by the PRKAG2 gene.- Function :AMP-activated protein kinase is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various... |
7q36 | CMH6 |
| TNNI3 TNNI3 Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene.-Interactions:TNNI3 has been shown to interact with PKD2L1, Troponin C type 1 and Polycystic kidney disease 2.-Further reading:- External links :*... |
19q13.4 | CMH7 |
| MYL3 MYL3 Myosin light chain 3 is a protein that in humans is encoded by the MYL3 gene.- External links :*... |
3p | CMH8 |
| TTN Titin Titin , also known as connectin, is a protein that in humans is encoded by the TTN gene. Titin is a giant protein that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured... |
2q24.3 | CMH9 |
| MYL2 MYL2 Myosin regulatory light chain 2, ventricular/cardiac muscle isoform is a protein that in humans is encoded by the MYL2 gene.- External links :* * Info with links in the... |
12q23-q24 | CMH10 |
| ACTC1 ACTC1 Actin, alpha cardiac muscle 1 is a protein that in humans is encoded by the ACTC1 gene.-Further reading:- External links :*... |
15q14 | CMH11 |
| CSRP3 CSRP3 Cysteine and glycine-rich protein 3 is a protein that in humans is encoded by the CSRP3 gene.- External links :*... |
11p15.1 | CMH12 |
About 50-60% of patients with a high index of clinical suspicion for HCM will have a mutation identified in at least 1 of 9 sarcomeric genes. Approximately 45% of these mutations occur in the β myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
heavy chain gene on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
14 q11.2-3, while approximately 35% involve the cardiac myosin binding protein C gene. Since HCM is typically an autosomal dominant trait, children of an HCM parent have 50% chance of inheriting the disease-causing mutation. Whenever a mutation is identified through genetic testing, family-specific genetic testing can be used to identify relatives at-risk for the disease (HCM Genetic Testing Overview). In individuals without a family history of HCM, the most common cause of the disease is a de novo mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
of the gene that produces the β-myosin heavy chain.
An insertion/deletion polymorphism in the gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
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
.
Children and cardiomyopathy
While much has been written about adults with HCM, information regarding children and cardiomyopathy is limited. At this point, it is estimated 30,000 children are affected by cardiomyopathy of all types (dilated, hypertrophic, restricted, etc.).Once HCM has been identified in a family, immediate testing of all family members will help to identify those at risk. Children often do not show signs of HCM; the first sign many children display is sudden cardiac arrest. Both invasive and non-invasive techniques exist to detect thickening of the left ventricle and other abnormalities associated with HCM. The most common non-invasive diagnostic test for detecting HCM is electrocardiography, though the most sensitive test for diagnosing HCM is genetic testing.
Beta blockers are often prescribed as the first medical treatment for HCM in children. Many options exist, so it is important to remember to inform one's doctor if undesirable side-effects occur so a switch can be made. Stopping a beta blocker treatment without the consent of your doctor is never advised.
Anatomic characteristics
Individuals with HCM have some degree of left ventricular hypertrophyLeft ventricular hypertrophy
Left ventricular hypertrophy is the thickening of the myocardium of the left ventricle of the heart.-Causes:While ventricular hypertrophy occurs naturally as a reaction to aerobic exercise and strength training, it is most frequently referred to as a pathological reaction to cardiovascular...
. 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
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
. 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
Systole (medicine)
Systole is the contraction of the heart. Used alone, it usually means the contraction of the left ventricle.In all mammals, the heart has 4 chambers. The left and right ventricles pump together. The atria and ventricles pump in sequence...
(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 valveMitral valve
The mitral valve is a dual-flap valve in the heart that lies between the left atrium and the left ventricle...
. 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
Venturi effect
The Venturi effect is the reduction in fluid pressure that results when a fluid flows through a constricted section of pipe. The Venturi effect is named after Giovanni Battista Venturi , an Italian physicist.-Background:...
—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 cannot 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 that at surgery are often "agglutinated" onto the LV anterior wall by abnormal attachments
.
The mid-septal bulge aggravates the malposition of the valve and redirects outflow so that it comes from a lateral and posterior direction. The abnormally directed outflow may be visualized behind and lateral to the enlarged mitral valve, where it catches it, and pushes it into the septum
.
There is a crucial overlap between the inflow and outflow portions of the left ventricle
.
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. An analogy is an open door in a drafty corridor: the door starts by moving slowly and then accelerates as it presents a greater surface area to the wind and finally it slams shut. The necessary conditions that predispose to SAM are: anterior position of the mitral valve in the LV, altered LV geometry that allows flow to strike the mitral valve from behind, and chordal slack
.
SAM may considered anteriorly directed mitral prolapse
.
In both conditions the mitral valve is enlarged and is displaced in systole by the pushing force of flow resulting in mitral regurgitation.
Because the mitral valve leaflet doesn't get pulled into the left ventricular outflow tract (LVOT) until after the aortic valve opens, the initial upstroke of the arterial pulse will be normal. When the mitral valve leaflet gets pushed into the LVOT, the arterial pulse will momentarily collapse and be followed by a second rise, as the left ventricular pressure overcomes the increased obstruction that SAM of the mitral valve causes. This can be seen on the physical examination as a double tap upon palpation of the apical impulse and as a double pulsation upon palpation of the carotid pulse, known as bifid pulse.
Associated symptoms
The clinical course of HCM is variable. Many patients are asymptomatic or mildly symptomatic. The symptomSymptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s of HCM include dyspnea (shortness of breath), chest pain (sometimes known as angina), uncomfortable awareness of the heart beat
Cardiac cycle
The cardiac cycle is a term referring to all or any of the events related to the flow or blood pressure that occurs from the beginning of one heartbeat to the beginning of the next. The frequency of the cardiac cycle is described by the heart rate. Each beat of the heart involves five major stages...
(palpitations), lightheadedness
Lightheadedness
Light-headedness is a common and often unpleasant sensation of dizziness and/or feeling that one may be about to faint, which may be transient, recurrent, or occasionally chronic. In some cases, the individual may feel as though his or her head is weightless. The individual may also feel as...
, fatigue, fainting (called syncope
Syncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
) and sudden cardiac death
Sudden Cardiac Death
Sudden cardiac death is natural death from cardiac causes, heralded by abrupt loss of consciousness within one hour of the onset of acute symptoms. Other forms of sudden death may be noncardiac in origin...
. Dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
is largely due to increased stiffness of the left ventricle, which impairs filling of the ventricles and leads to elevated pressure in the left ventricle and left atrium. Symptoms are not closely related to the presence or severity of an outflow tract gradient. Often, symptoms mimic those of congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
(esp. activity intolerance & dyspnea), but 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
Supraventricular tachycardia
Supraventricular tachycardia is a general term that refers to any rapid heart rhythm originating above the ventricular tissue. Supraventricular tachycardias can be contrasted to the potentially more dangerous ventricular tachycardias - rapid rhythms that originate within the ventricular...
or ventricular tachycardia
Ventricular tachycardia
Ventricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...
, ventricular septal wall thickness over 3 cm, hypotensive response to exercise, recurrent syncope
Syncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
(especially in children), and bradyarrhythmias (slow rhythms of the heart).
Physical examination
| Aortic stenosis | Hypertrophic cardiomyopathy | |
|---|---|---|
| Echocardiography | ||
| Aortic valve calcification | Common | No |
| Dilated ascending aorta | Common | Rare |
| Ventricular hypertrophy | Concentric LVH Left ventricular hypertrophy Left ventricular hypertrophy is the thickening of the myocardium of the left ventricle of the heart.-Causes:While ventricular hypertrophy occurs naturally as a reaction to aerobic exercise and strength training, it is most frequently referred to as a pathological reaction to cardiovascular... |
Asymmetric, often involving the septum |
| Physical examination | ||
| Murmur of AI Aortic insufficiency Aortic insufficiency , also known as aortic regurgitation , is the leaking of the aortic valve of the heart that causes blood to flow in the reverse direction during ventricular diastole, from the aorta into the left ventricle.... |
Common | No |
| Pulse pressure after PVC Premature ventricular contraction A premature ventricular contraction , also known as a premature ventricular complex, ventricular premature contraction , ventricular premature beat , or extrasystole, is a relatively common event where the heartbeat is initiated by the heart ventricles rather than by the sinoatrial node, the... |
Increased | Decreased |
| Valsalva maneuver Valsalva maneuver The Valsalva maneuver or Valsalva manoeuvre is performed by moderately forceful attempted exhalation against a closed airway, usually done by closing one's mouth and pinching one's nose shut... |
Decreased intensity of murmur | Increased intensity of murmur |
| Carotid pulsation | Normal or tardus et parvus Pulsus tardus et parvus In medicine, pulsus tardus et parvus, also pulsus parvus et tardus, slow-rising pulse and anacrotic pulse, is a sign where, upon palpation, the pulse is weak/small , and late relative to its usually expected character.... |
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 is often present with this disease.
Upon auscultation
Auscultation
Auscultation is the term for listening to the internal sounds of the body, usually using a stethoscope...
, the cardiac murmur
Heart sounds
Heart sounds, or heartbeats, are the noises generated by the beating heart and the resultant flow of blood through it...
will sound similar to the murmur of aortic stenosis. However, a murmur due to HCM 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
Valsalva maneuver
The Valsalva maneuver or Valsalva manoeuvre is performed by moderately forceful attempted exhalation against a closed airway, usually done by closing one's mouth and pinching one's nose shut...
). Classically, the murmur is also loudest at the left parasternal edge, 4th intercostal space, rather than in the aortic area.
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 contraction
Premature ventricular contraction
A premature ventricular contraction , also known as a premature ventricular complex, ventricular premature contraction , ventricular premature beat , or extrasystole, is a relatively common event where the heartbeat is initiated by the heart ventricles rather than by the sinoatrial node, the...
s (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. However, the murmur intensity increases with both Aortic Stenosis and HCM post-PVC.
Screening
HCM is frequently asymptomatic until sudden cardiac deathSudden Cardiac Death
Sudden cardiac death is natural death from cardiac causes, heralded by abrupt loss of consciousness within one hour of the onset of acute symptoms. Other forms of sudden death may be noncardiac in origin...
, and is the leading cause of sudden cardiac death in young athletes. HCM can be detected with an echocardiogram with 80%+ accuracy, which can be preceded by screening with an electrocardiogram
Electrocardiogram
Electrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...
(ECG) to test for heart abnormalities. History and physical examination alone are ineffective, giving warning of heart abnormalities in only 3% of patients before sudden cardiac death. One study found that the incidence of sudden cardiovascular death in young competitive athletes declined in the Veneto region of Italy by 89% since introduction of routine Hypertrophic Cardiomyopathy Screening
Hypertrophic Cardiomyopathy Screening
Hypertrophic cardiomyopathy, or HCM, is the leading cause of sudden cardiac death in young athletes. HCM is frequently asymptomatic until SCD, and thus its prevention requires screening. Screening by medical history and physical exam are ineffective, indicating heart abnormalities in only 3% of...
of athletes.
United States
There are several potential challenges associated with routine screening for HCM in the United States. First, the U.S. athlete population of 15 million is almost twice as large as Italy's estimated athlete population. Second, these events are extremely rare in the U.S., with fewer than 100 deaths due to HCM in competitive athletes per year, or about 1 death per 220,000 athletes.In the United States such screening is not routine and the American Heart Association
American Heart Association
The American Heart Association is a non-profit organization in the United States that fosters appropriate cardiac care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke. It is headquartered in Dallas, Texas...
has "consistently opposed" routine screening.
Diagnostic testing
A diagnosisMedical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
of hypertrophic cardiomyopathy is based upon a number of features of the disease process. While there is use of echocardiography, cardiac catheterization
Cardiac catheterization
Cardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done for both investigational and interventional purposes...
, or cardiac MRI in the diagnosis of the disease, other important factors include ECG
Electrocardiogram
Electrocardiography is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body...
and genetic test findings and if there is any family history of HCM or unexplained sudden death in otherwise healthy individuals.
Cardiac catheterization
Cardiac catheterization
Cardiac catheterization is the insertion of a catheter into a chamber or vessel of the heart. This is done for both investigational and interventional purposes...
, catheter
Catheter
In medicine, a catheter is a tube that can be inserted into a body cavity, duct, or vessel. Catheters thereby allow drainage, administration of fluids or gases, or access by surgical instruments. The process of inserting a catheter is catheterization...
s can be placed in the left ventricle and the ascending aorta
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...
, to measure the pressure difference between these structures. In normal individuals, during ventricular systole
Systole (medicine)
Systole is the contraction of the heart. Used alone, it usually means the contraction of the left ventricle.In all mammals, the heart has 4 chambers. The left and right ventricles pump together. The atria and ventricles pump in sequence...
, 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
Premature ventricular contraction
A premature ventricular contraction , also known as a premature ventricular complex, ventricular premature contraction , ventricular premature beat , or extrasystole, is a relatively common event where the heartbeat is initiated by the heart ventricles rather than by the sinoatrial node, the...
(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. In those patients deemed to be at high risk, the benefits and infrequent complications of implantable cardioverter defibrillator (ICD) therapy are discussed; devices have been implanted in as many as 15% of patients at HCM centers. The ICD is the most effective and reliable treatment option available, harboring the potential for absolute protection and altering the natural history of this disease in some patients. Treatment of symptoms of obstructive HCM is directed towards decreasing the left ventricular outflow tract gradient and symptoms of dyspnea, chest pain and syncope. Medical therapy is successful in the majority of patients. The first medication that is routinely used is a beta-blocker (metoprololMetoprolol
Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate...
, atenolol, bisoprolol
Bisoprolol
Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker. The FDA approved Duramed Pharmaceutical's application for Zebeta Oral Tablets as a new molecular...
, propranolol). If symptoms and gradient persist, disopyramide
Disopyramide
Disopyramide is an antiarrhythmic medication. It is a Class Ia antiarrhythmic used in the treatment of ventricular tachycardias...
may be added to the beta-blocker.
Alternately a calcium channel blocker such as verapamil
Verapamil
Verapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...
may be substituted for a beta blocker. It should be stressed that most patients' symptoms may be managed medically without needing to resort to interventions 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 is 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 myectomySeptal myectomy
Septal myectomy is a cardiac surgery treatment for hypertrophic cardiomyopathy . The surgery entails removing a portion of the septum that is obstructing the flow of blood from the left ventrical to the aorta. Septal myectomies have been successfully performed for more than 25 years...
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 less than 1%. It involves a median sternotomy (general anesthesia, opening the chest, and cardiopulmonary bypass) and removing a portion of the interventricular septum. Surgical myectomy resection focused just on the subaortic septum, to increase the size of the outflow tract to reduce Venturi forces may be inadequate to abolish systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. With this limited sort of resection the residual mid-septal bulge still redirects flow posteriorly: SAM persists because flow still gets behind the mitral valve. It is only when the deeper portion of the septal bulge is resected that flow is redirected anteriorly away from the mitral valve, abolishing SAM.
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 ablationAlcohol septal ablation
Alcohol septal ablation is a percutaneous, minimally-invasive treatment performed by an interventional cardiologist to relieve symptoms and improve functional status in severely symptomatic patients with hypertrophic cardiomyopathy who meet strict clinical, anatomic and physiologic selection...
, 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
Coronary circulation
Coronary circulation is the circulation of blood in the blood vessels of the heart muscle . The vessels that deliver oxygen-rich blood to the myocardium are known as coronary arteries...
. This is a technique with results similar to the surgical septal myectomy procedure but is less invasive, since it does not 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
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, 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 pacemakerArtificial pacemaker
A pacemaker is a medical device that uses electrical impulses, delivered by electrodes contacting the heart muscles, to regulate the beating of the heart...
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 diseaseHeart disease
Heart disease, cardiac disease or cardiopathy is an umbrella term for a variety of diseases affecting the heart. , it is the leading cause of death in the United States, England, Canada and Wales, accounting for 25.4% of the total deaths in the United States.-Types:-Coronary heart disease:Coronary...
in cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s; the disease process and genetics are believed to be similar to the disease in human
Human
Humans are the only living species in the Homo genus...
s. In Maine Coon
Maine Coon
The Maine Coon is a breed of domestic cat with a distinctive physical appearance and valuable hunting skills. It is one of the oldest natural breeds in North America, specifically native to the state of Maine, where it is the official State Cat....
and American Shorthair
American Shorthair
The American Shorthair is a breed of cat believed to be descended from European domestic cats brought to North America by early settlers to protect valuable cargo from mice and rats...
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
Maine Coon
The Maine Coon is a breed of domestic cat with a distinctive physical appearance and valuable hunting skills. It is one of the oldest natural breeds in North America, specifically native to the state of Maine, where it is the official State Cat....
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 identified in Maine Coon cats has not been found in any other breed of cat with HCM but more recently another myosin binding protein C mutation has been identified in Ragdoll cats with HCM.
Turkish Angoras also may be susceptible to HCM because of this gene. The CatScan study performed at the Royal Veterinary College
Royal Veterinary College
The Royal Veterinary College is a veterinary school located in London, United Kingdom and a constituent college of the federal University of London. The RVC was founded in 1791 and joined the University of London in 1949...
, London, is looking at the prevalence of the disease within a normal population of apparently healthy domestic cats (non-pedigree). This study has just begun (October 2009) and the results of should be available in early 2012.
While there is no cure for HCM, early detection and regular echocardiograms are key to trying to ward off life-threatening problems. 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. While medication is commonly given to cats with HCM that have no clinical signs, no medication has been shown to be helpful at this stage and it has been shown that an ACE inhibitor is not beneficial until heart failure is present (at which time a diuretic is most beneficial). Diltiazem generally produces no demonstrable benefit. Atenolol is commonly administered when systolic anterior motion of the mitral valve is present.
Thromboembolic disease (TED) is relatively common sequelae of Feline HCM. The aetiology remains a little uncertain, but it is thought that ischemic damage to the hypertrophied left ventricular myocardium facilitates thrombus formation and subsequent embolism. Classically the embolus lodges at the iliac bifurcation of the aorta, occluding either one or both of the common iliac arteries. Clinically this presents as a cat with complete loss of function in one or both hindlimbs. The hindlimbs are cold, and the cat is in considerable pain. This pain derives from the exaggerated inflammatory response to the embolus at the point of impact, and the inflammatory mediators released generally have a vasoconstrictor effect further exacerbating the problem. Emboli may, rarely, lodge in other locations, typically the renal or ovarian/testicular arteries as they exit the abdominal aorta.
Treatment of TED is variable - typically very low doses of aspirin may be prescribed (aspirin however is extremely toxic to cats and should only be prescribed and administered by a veterinary surgeon). Plavix is also another widely used drug that may or may not prevent clot formation in HCM cats. The FATCAT study at Purdue University is addressing the efficacy of aspirin vs. Plavix for the prevention of a second clot in cats that have already experienced a clot. Thrombolytic agents (e.g., tissue plasminogen activators) have been used successfully, but their cost is usually prohibitively high in veterinary medicine. Despite the relative efficacy of treatment, the prognosis for cats with TED is poor as they are likely to have significant HCM already, and a recurrent bout of TED is very likely. For this reason euthanasia is often considered in TED cats.
Notable people
After the death of Marc-Vivien FoéMarc-Vivien Foé
Marc-Vivien Foé was a Cameroonian international footballer, who played in midfield for both club and country. With success in the French League, and stints in the English Premier League, his sudden death, while in the middle of an international competitive fixture, came as a shock to the worldwide...
of Cameroon during a 2003 FIFA Confederations Cup
FIFA Confederations Cup
The FIFA Confederations Cup is an association football tournament for national teams, currently held every four years by FIFA. It is contested by the winners of each of the six FIFA confederation championships , along with the FIFA World Cup winner and the host nation, to bring the number of teams...
match, his autopsy revealed hypertrophic cardiomyopathy. Miklós "Miki" Fehér
Miklós Fehér
Miklós "Miki" Fehér was a Hungarian footballer who played as a striker.On 25 January 2004, Fehér died of a cardiac arrest during a match between Vitória de Guimarães and his team Benfica in Guimarães, Portugal....
, a Hungarian football player who died during a match on January 25, 2004, also suffered from HCM.
Other noted athletes believed or suspected to have died from HCM include NFL
National Football League
The National Football League is the highest level of professional American football in the United States, and is considered the top professional American football league in the world. It was formed by eleven teams in 1920 as the American Professional Football Association, with the league changing...
players Thomas Herrion
Thomas Herrion
Thomas Herrion was an American football player for the San Francisco 49ers. Born in Fort Worth, Texas, Herrion, a 6-foot-3 , 310-pound guard, played college football first at Kilgore College at the junior college level before transferring to the University of Utah where he blocked for current...
, Mitch Frerotte
Mitch Frerotte
Paul Mitchael Frerotte was an American professional football player who played as a guard for four seasons in the National Football League, all with the Buffalo Bills. Frerotte is perhaps best known for scoring three touchdowns during the 1992 NFL season, a record for an offensive lineman.Frerotte...
, Damien Nash
Damien Nash
Damien Darnell Nash was an American football player who was a running back for the Denver Broncos of the National Football League. He died after the 2006-2007 season, his only season with the Broncos....
, Gaines Adams
Gaines Adams
Gaines Adams was an American football defensive end in the National Football League. He was drafted by the Tampa Bay Buccaneers in the first round in the 2007 NFL Draft and in 2009 was traded to the Chicago Bears...
, and Derrick Faison; NBA
National Basketball Association
The National Basketball Association is the pre-eminent men's professional basketball league in North America. It consists of thirty franchised member clubs, of which twenty-nine are located in the United States and one in Canada...
players Reggie Lewis
Reggie Lewis
Reggie Lewis was an American professional basketball player for the NBA's Boston Celtics from 1987 to 1993.-Early life:...
, Jason Collier
Jason Collier
Jason Jeffrey Collier was an American professional basketball player in the NBA. At death, the tall center Collier weighed...
, and Kevin Duckworth
Kevin Duckworth
Kevin Jerome Duckworth was an American professional basketball player at center in the National Basketball Association. A native of Illinois, he played college basketball at Eastern Illinois University before being drafted in 1986 in the second round by the San Antonio Spurs...
; NHL
National Hockey League
The National Hockey League is an unincorporated not-for-profit association which operates a major professional ice hockey league of 30 franchised member clubs, of which 7 are currently located in Canada and 23 in the United States...
player Sergei Zholtok
Sergei Zholtok
Sergejs Žoltoks was a Latvian professional ice hockey center who played ten seasons in the National Hockey League for the Boston Bruins, Ottawa Senators, Montreal Canadiens, Edmonton Oilers, Minnesota Wild and Nashville Predators....
; baseball
Baseball
Baseball is a bat-and-ball sport played between two teams of nine players each. The aim is to score runs by hitting a thrown ball with a bat and touching a series of four bases arranged at the corners of a ninety-foot diamond...
pitcher Joe Kennedy; long distance runner Ryan Shay
Ryan Shay
Ryan Shay was an American professional long-distance runner. He was born in Ypsilanti, Michigan, and attended the University of Notre Dame. He was married to Alicia Craig, also an American distance runner...
; Loyola Marymount basketball star Hank Gathers
Hank Gathers
Eric "Hank" Gathers was an American college basketball star at Loyola Marymount University who collapsed and died during a game. He was the second player in NCAA Division I history to lead the nation in scoring and rebounding in the same season...
; Loyola Marymount soccer player David Kucera; NFL Defensive End Kansas State
Kansas State Wildcats football
The Kansas State Wildcats football program is the intercollegiate football program of the Kansas State University Wildcats. The program is classified in the NCAA's Division I Bowl Subdivision, and the team competes in the Big 12 Conference...
football player Anthony Bates; OHL
OHL
OHL may refer to:*Oberste Heeresleitung, the Supreme Army Command of Germany in World War I*Obrascón Huarte Lain, a Spanish construction company*Old Hill railway station's National Rail station code*Ontario Hockey League...
Windsor Spitfires
Windsor Spitfires
The Windsor Spitfires are a junior ice hockey team in the Ontario Hockey League. The team is based in Windsor, Ontario, Canada. The franchise was granted for the 1975–76 season and revived a previous OHA Jr. A Spitfires team which moved to become the Hamilton Tiger Cubs in 1953.-History:The...
captain Mickey Renaud; and Russian ice hockey
Ice hockey
Ice hockey, often referred to as hockey, is a team sport played on ice, in which skaters use wooden or composite sticks to shoot a hard rubber puck into their opponent's net. The game is played between two teams of six players each. Five members of each team skate up and down the ice trying to take...
star Alexei Cherepanov
Alexei Cherepanov
Alexei Andreyevich Cherepanov was a Russian professional ice hockey winger who played for Avangard Omsk of the Kontinental Hockey League . The New York Rangers of the National Hockey League drafted Cherepanov with their first selection, seventeenth overall, in the 2007 NHL Entry Draft...
. Jesse Marunde
Jesse Marunde
Jesse Marunde was an American strongman athlete who placed second in the 2005 World's Strongest Man competition....
, an American strongman
Strongman (strength athlete)
In the 19th century, the term strongman referred to an exhibitor of strength or circus performers of similar ilk who displayed feats of strength such as the bent press , supporting large amounts of...
, died of HCM in 2007 after a workout at his gym.
On December 10, 2008, NBA player Cuttino Mobley
Cuttino Mobley
Cuttino Rashawn Mobley is a former American professional basketball shooting guard who played from 1998 to 2008 in the National Basketball Association .-Biography:...
announced his retirement due to worsening HCM. The disease also ended the career of former Wake Forest
Wake Forest Demon Deacons men's basketball
The Wake Forest Demon Deacons men's basketball team participates in the Atlantic Coast Conference and their homecourt is the Lawrence Joel Veterans Memorial Coliseum. Their only Final Four appearance was in 1962 and through the years they have produced several NBA players. The Demon Deacons have...
star Robert O'Kelley, after a mandatory EKG in Brazil discovered his condition in 2006.
British comedy actor Leonard Rossiter
Leonard Rossiter
Leonard Rossiter was an English actor known for his roles as Rupert Rigsby, in the British comedy television series Rising Damp , and Reginald Iolanthe Perrin, in The Fall and Rise of Reginald Perrin...
died from hypertrophic cardiomyopathy in 1984 while waiting to go onstage at the Lyric Theatre, London. The autopsy of actor Corey Haim
Corey Haim
Corey Ian Haim was a Canadian actor, known for a 1980s Hollywood career as a teen idol. He starred in a number of films such as Lucas, Silver Bullet, Murphy's Romance, License to Drive and Dream a Little Dream...
identified HCM as one of the contributing causes (along with pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
and coronary arteriosclerosis
Arteriosclerosis
Arteriosclerosis refers to a stiffening of arteries.Arteriosclerosis is a general term describing any hardening of medium or large arteries It should not be confused with "arteriolosclerosis" or "atherosclerosis".Also known by the name "myoconditis" which is...
) for his death in 2010. American pornographic actress Aurora Jolie also has HCM.
Fictional characters
In the CWThe CW Television Network
The CW Television Network is a television network in the United States launched at the beginning of the 2006–2007 television season. It is a joint venture between CBS Corporation, the former owners of United Paramount Network , and Time Warner's Warner Bros., former majority owner of The WB...
television show One Tree Hill
One Tree Hill (TV series)
One Tree Hill is an American television drama created by Mark Schwahn, which premiered on September 23, 2003, on The WB Television Network. After its third season, The WB merged with UPN to form The CW Television Network, and, since September 27, 2006, the network has been the official broadcaster...
, characters Dan and Lucas Scott
Lucas Scott
Lucas Eugene Scott is a fictional character and formerly the main protagonist from The CW television series One Tree Hill, portrayed by Chad Michael Murray. Lucas is a talented basketball player and writer. He is rival to half-brother Nathan Scott, before the two eventually become close friends...
have HCM.
In the Fox
Fox Broadcasting Company
Fox Broadcasting Company, commonly referred to as Fox Network or simply Fox , is an American commercial broadcasting television network owned by Fox Entertainment Group, part of Rupert Murdoch's News Corporation. Launched on October 9, 1986, Fox was the highest-rated broadcast network in the...
series Beverly Hills 90210, Joe Bradley, a quarterback for California University and boyfriend of Donna Martin for much of season 6, is diagnosed with HCM by Donna's father, Dr. John Martin.
Vivian Johnson
Vivian Johnson (Without a Trace)
Special Agent Vivian "Viv" Johnson is a fictional character played by British actress Marianne Jean-Baptiste on the CBS TV drama Without a Trace. Vivian is second in command of the FBI missing persons case squad in New York City...
on Without a Trace
Without a Trace
Without a Trace is an American television drama which originally ran on CBS from September 26, 2002 to May 19, 2009. The series was set in New York City and concerned a fictitious FBI Missing Persons Unit.-Premise:...
also has HCM.
Willie Cager in Glory Road
Glory Road (film)
Glory Road is an American sports film directed by James Gartner, based on a true story dealing with the events leading to the 1966 NCAA Men's Division I Basketball Championship, in which the late Don Haskins – played by Josh Lucas – head coach of the Texas Western College led a team...
was benched with HCM.
The main character of the 1997 film The Sixth Man
The Sixth Man
The 6th Man is a supernatural sports comedy starring Marlon Wayans and Kadeem Hardison. The film was directed by Randall Miller. The film features real NCAA schools, although the rosters are fictitious...
, Antoine Taylor, played by actor Kadeem Hardison
Kadeem Hardison
Kadeem Hardison is an American actor. He is best known for his role as Dwayne Wayne on A Different World, a spin-off of the long-running NBC sitcom The Cosby Show.-Childhood:...
, died from HCM.
In the Australian TV series Love My Way
Love My Way
Love My Way was a Logie Award winning and critically acclaimed Australian television drama series. It won the AFI award for Best Television Drama Series for each of its three seasons ....
, Frankie and Charlie's daughter, Lou, dies suddenly from HCM.
In an episode of Eli Stone
Eli Stone
Eli Stone is an American TV series, and also the name of the title character.San Francisco lawyer Eli Stone begins to see things, which leads him to discover a brain aneurysm...
(10/21/2008) the character Grace Fuller played by Katie Holmes
Katie Holmes
Katherine Noelle "Katie" Holmes is an American actress who first achieved fame for her role as Joey Potter on The WB television teen drama Dawson's Creek from 1998 to 2003. Her movie roles have included the blockbuster Batman Begins along with art house films such as The Ice Storm and thrillers...
has HCM.
The lead girl in the Korean Movie A Millionaire's First Love
A Millionaire's First Love
A Millionaire's First Love is a Korean romance film released in 2006. It stars Hyun Bin and Lee Yeon Hee . Theme of this movie is "Nothing is more important than the true love of your heart."-Plot:...
played by Lee Yeon Hee died from HCM.
External links
- Hypertrophic Cardiomyopathy Association
- GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview
- Cardiomyopathy Association
- Information from the Stanford Hypertrophic Cardiomyopathy Center
- Hypertrophic Cardiomyopathy Research Foundation
- Physician's Guide to Treating HCM
- MedPix
- Feline Hypertrophic Cardiomyopathy
- Cleveland Clinic Hypertrophic Cardiomyopathy Information Page
- Dr. William Spencer of the Medical University of South Carolina discusses minimally invasive treatment for treating Hypertrophic Cardiomyopathy in this video
- "New Concepts in the Control of Muscle Contraction" by Gerry A Smith PhD (Cantab)
- Felipedia