Hypertrophic cardiomyopathy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

The first case of hypertrophic cardiomyopathy (HCM) was described by in 1869 Henri Liouville in the Gazette Medecine Paris. In 1907 Dr. A. Schmincke, a German pathologist, described two hearts with left ventricular hypertrophy; both came from women in their mid-fifties. Levy and von Glahn in 1944, from Colombia University in New York, published a series of cases which resembles HCM. In 1949, William Evans, a London cardiologist, described familial occurrence of cardiac hypertrophy in a series of patients which were similar to those described in the paper by Levy and von Glahn. In 1961 Paré et al. reported thirty members of five generations of a French Canadian family in Quebec in whom the condition was inherited in an autosomal dominant manner. In 1958 Teare, an English pathologist, described eight cases of asymmetric cardiac muscle hypertrophy, he thought that they might be benign cardiac tumors. Seven of these caused sudden death in young adults. Teare named the condition “Asymetrical Hypertrophy of the Heart.” In 1959 Sir Russell Brock described a young man with angina and a subaortic stenosis and a subaortic intraventricular pressure gradient. Morrow and Braunwald published their first report in the same year, followed by several other reports. The sudden cardiac deaths of 387 young American athletes (under age 35) were analyzed in a 2003 medical review, and HCM was the leading cause of sudden cardiac death in athletes. In 1961, Morrow described a surgical procedure to relieve the obstruction, which is still the most widely used method of surgical treatment. In 1962, with respect to the observed intensification of obstruction in HCM with the beta-adrenergic agonists, Braunwald suggested the use of newly developed beta-blockers. In 1964, Braunwald reported beta-blockers beneficial hemodynamic effects. 1967, the clinical benefits of treatment with beta blockers in patients with HCM has been proved to the scientific society.

• The first case of hypertrophic cardiomyopathy (HCM) was described by in 1869 Henri Liouville in the Gazette Medecine Paris. He described a 75-year-old woman who developed worsening dyspnea over several days. On physical examination, she had a systolic heart murmur. She died shortly after the presentation.^[1] Liouville H. Rétrécissement cardiaque sous aortique. Gazette Medecine Paris. 1869;24:161–163.

• In 1907 Dr. A. Schmincke, a German pathologist, described two hearts with left ventricular hypertrophy; both came from women in their mid fifties. ^[1]Schmincke A. Ueber linkseitige muskulose conustenosen. Deutsche Med Wochenschr. 1907;33:2082–2085.
• Levy and von Glahn in 1944, from Colombia University in New York, published a series of cases which resembles HCM.^[1] Levy RL, von Glahn WC. Cardiac hypertrophy of unknown cause. A study of the clinical and pathologic features in ten adults. Am Heart J. 1944;28:714–741.
• In 1949, William Evans, a London cardiologist, described familial occurrence of cardiac hypertrophy in a series of patients which were similar to those described in the paper by Levy and von Glahn. ^[2]
• In 1961 Paré et al. reported thirty members of five generations of a French Canadian family in Quebec in whom the condition was inherited in an autosomal dominant manner.^[3]
• In 1958 Teare, an English pathologist, described eight cases of asymmetric cardiac muscle hypertrophy, he thought that they might be benign cardiac tumors. Seven of these caused sudden death in young adults. Teare named the condition “Asymetrical Hypertrophy of the Heart.”^[4]
• In 1959 Sir Russell Brock described a young man with angina and a subaortic stenosis and a subaortic intraventricular pressure gradient. He mentioned: “That this is not an isolated case is made clear by the experience of Dr. Glenn Morrow who tells me he has operated on two similar cases in two young men in their early twenties; both survived. He has kindly allowed me to mention these prior to his own report of them (Morrow and Braunwald, Circulation, in press, 1959).” ^[5]
• Morrow and Braunwald published their first report in the same year, followed by several other reports. ^[6]

• In 1961, Morrow described a surgical procedure (myectomy) to relieve the obstruction,^[7] which is still the most widely used method of surgical treatment.

• In 1962, with respect to the observed intensification of obstruction in HCM with the beta-adrenergic agonists,^[8] Braunwald suggested the use of newly developed beta-blockers.
• In 1964, Braunwald reported beta-blockers beneficial hemodynamic effects.^[9]

• In 1967, the clinical benefits of treatment with beta-blockers in patients with HCM has been proved to the scientific society. ^[10][11][1]

The following are a few famous cases of hypertrophic cardiomyopathy:

• Sir David Paradine Frost: A post-mortem following the death of popular TV presenter David Frost in 2013 showed he suffered from HCM, though it didn’t contribute to his death and his family wasn’t informed. The sudden cardiac death of his 31-year-old son in 2015 led the family to collaborate with the British Heart Foundation to raise funds for better screening.
• The sudden cardiac deaths of 387 young American athletes (under age 35) were analyzed in a 2003 medical review, and HCM was the leading cause of sudden cardiac death in athletes.^[12] Hence, there is a lengthy list of athletes that passed away because of HCM, among them are:

• Reggie Lewis, Baltimore Basketball Player
• Gaines Adams, American professional football player
• Heath Benedict, Dutch-American professional football player
• James Victor Cain, American professional football player
• Mitchell Cole, English footballer (Soccer)

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Editors-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

There are two variants of hypertrophic cardiomyopathy: an obstructive variant, and a non-obstructive variant. About 25% of individuals with hypertrophic cardiomyopathy (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). If left ventricular outflow obstruction is present, then this syndrome has been known as wide variety of terms including: hypertrophic cardiomyopathy or HCM, asymmetric septal hypertrophy or ASH, hypertrophic obstructive cardiomyopathy, HOCM, idiopathic hypertrophic subaortic stenosis or IHSS.

A non-obstructive variant of HCM is known as apical hypertrophic cardiomyopathy , which is also known as nonobstructive hypertrophic cardiomyopathy and Japanese variant hypertrophic cardiomyopathy or the Yamaguchi variant (since the first cases described were all in individuals of Japanese descent), also known as apical hypertrophic cardiomyopathy (ApHCM) or Yamaguchi syndrome.

About 25% of individuals with hypertrophic cardiomyopathy (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). If left ventricular outflow obstruction is present, then this syndrome has been known as wide variety of terms including: hypertrophic cardiomyopathy or HCM, asymmetric septal hypertrophy or ASH, hypertrophic obstructive cardiomyopathy, HOCM, idiopathic hypertrophic subaortic stenosis or IHSS, familial isolated hypertrophic obstructive cardiomyopathy, familial isolated hypertrophic subaortic stenosis, familial or idiopathic hypertrophic subaortic stenosis, familial or idiopathic hypertrophic obstructive cardiomyopathy, primitive hypertrophic obstructive cardiomyopathy, primitive hypertrophic subaortic stenosis.

A non-obstructive variant of HCM is known as apical hypertrophic cardiomyopathy ^[1], which is also known as nonobstructive hypertrophic cardiomyopathy and Japanese variant hypertrophic cardiomyopathy or the Yamaguchi variant (since the first cases described were all in individuals of Japanese descent), also known as apical hypertrophic cardiomyopathy (ApHCM) or Yamaguchi syndrome.

• Ace of spade observation in echocardiography is pathognomonic of apical hypertrophy.

• Nevertheless, hypertrophic non-obstructive cardiomyopathy can either be familial or sporadic. It has been shown that a number of chronic medical conditions might be contributed to HNCM development such as thyroid disease, diabetes, and obesity.

• Mutations in several genes (MYH7, MYBPC3, TNNT2, and TNNI3 genes) cause the inherited form of hypertrophic cardiomyopathy.
• This is an autosomal dominant familial disorder.
• HNCM can potentially evolve into:

• Hypertrophic obstructive cardiomyopathy
• Heart valve regurgitation
• Aberrant heartbeats (arrhythmia)
• Sudden cardiac arrest
• Dilated cardiomyopathy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, Soroush Seifirad, M.D.[2]

The progression to hypertrophic cardiomyopathy usually involves the mutations in contractile sarcomeric proteins of myocardium, which describe the presence of left ventricular hypertrophy (LVH) in the absence of an increased external load (unexplained LVH). Additionally, HCM hypertrophy is generally asymmetric.

HCM is the most common genetically transmitted cardiovascular disease. 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. Penetrance of HCM is incomplete, variable and time or age-related. The disease may be sporadic but affected family members are discovered in 13% of cases. More than 200 mutations involving at least 10 chromosomes encoding structural proteins of the myocyte have been discovered. These mutations have varying degrees of penetrance and even the same mutation may have variable expression, implying the superimposed effects of other genes or environmental influences. Children of a patient with HCM have a 50% chance of inheriting the trait.

Depending on the degree of obstruction of the outflow of blood from the left ventricle of the heart, HCM can be defined as obstructive or non-obstructive. 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).

Although there may be structural or functional obstruction of the left ventricular outflow tract, symptoms may arise more often from diastolic dysfunction.There is extensive periarteriolar fibrosis that results in microvascular dysfunction and impairment in coronary flow reserve in patients with hypertrophic obstructive cardiomyopathy. Individuals with HCM have some degree of left ventricular hypertrophy. In approximately 2/3rds of cases this is asymmetric hypertrophy, involving the interventricular septum, and is known as asymmetric septal hypertrophy (ASH). This is in contrast to the symmetric and concentric hypertrophy seen in aortic stenosis or hypertension. On histopathologic examination, hypertrophic cardiomyopathy is characterized by both myocardial disarrays and by periarteriolar fibrosis. Myocardial disarray can be associated with aberrant impulse conduction and arrhythmias, and periarteriolar fibrosis can be associated with myocardial ischemia.

The normal physiology of myocardium can be understood as follows:

• The myocardium is composed of specialized cardiac muscle cells with an ability not possessed by muscle tissue elsewhere in the body. Cardiac muscle, like other muscles, can contract, but it can also carry an action potential (i.e. conduct electricity), like the neurones that constitute nerves.

• The progression to Hypertrophic cardiomyopathy usually involves the mutations in contractile sarcomeric proteins of myocardium, which describe the presence of left ventricular hypertrophy (LVH) in the absence of an increased external load (unexplained LVH).
• Additionally, HCM hypertrophy is generally asymmetric.

Hypertrophic cardiomyopathy is transmitted in an autosomal dominant pattern.

Genes involved in the pathogenesis of hypertrophic cardiomyopathy include:

• MYH7
• TNNT2
• TPM1

The development of hypertrophic cardiomyopathy is the result of multiple genetic mutations such as:

• Beta-myosin heavy chain
• Myosin binding protein C
• Cardiac troponin T

HCM is the most common genetically transmitted cardiovascular disease. 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. ^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]} Penetrance of HCM is incomplete, variable and time or age-related. The disease may be sporadic but affected family members are discovered in 13% of cases. More than 200 mutations involving at least 10 chromosomes encoding structural proteins of the myocyte have been discovered. These mutations have varying degrees of penetrance and even the same mutation may have variable expression, implying superimposed effects of other genes or environmental influences. Children of a patient with HCM have a 50% chance of inheriting the trait.

Mutations in three regions affect more than half the patients with HCM:

• Beta-myosin heavy chain
• Myosin binding protein C
• Cardiac troponin T

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. Specific gene mutations that have been identified include the following:

While the above table represents the most common genetic mutations, there are also about 200 intergenic (within a gene) mutations. These include missense and single amino acid residue substitutions. There are different genetic mutations in different families. The environment may also play a role because affected individuals in the same family may have a different phenotypic expression (i.e different degrees of left ventricular hypertrophy). The goal of modifier genes in regulating phenotypic expression is not clear.

While genes, gene modifiers, and environment may play a role in the phenotypic expression of left ventricular hypertrophy, genes may also play a role in the risk of arrhythmias. While most literature so far focuses on European, American, and Japanese populations, HCM appears in all races. The incidence of HCM is about 0.2% to 0.5% of the general population.

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. This chromosomal abnormality accounts for approximately 35%-45% of HCM cases. Significant LVH (left ventricular hypertrophy) is usually present. The Arg403Gln mutation is associated with an extremely poor prognosis with an average age of death at 33 years, while the Val606Met mutation is associated with a better prognosis.

Accounts for approximately 15% of cases. Substantially less hypertrophy is noted but histology demonstrates the characteristic myocyte disarray of HCM. Most mutations of this gene are associated with markedly reduced survival.

This chromosomal abnormality accounts for 15% to 35% of patients, but given the reduced penetrance associated with this abnormality, the true incidence may actually be greater. Patients generally present later in life and in general, have a better prognosis than beta myosin heavy chain or cardiac troponin T mutations. Up to 60% of patients at age 50 years have no evidence of LVH. LVH may appear later in life in these patients. Because of this, a normal EKG and a normal echocardiography at age 18 does not exclude the presence of HCM.

The beta-myosin heavy chain Arg663 His mutation is associated with a higher risk of atrial fibrillation. ^[16]

There is no myocyte disarray, but the conduction block is present. This variant is more akin to a storage disease.^[17]

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. ^{[18] [19]}

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.

Depending on the degree of obstruction of the outflow of blood from the left ventricle of the heart, HCM can be defined as obstructive or non-obstructive. 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).

The left ventricular obstruction can be either

• Mid-cavitary: the middle of the ventricle or
• Sub-aortic: just below the aortic valve

The valve gradient in HCM can be classified into three categories:

1. A gradient greater than 30 mm Mercury under basal conditions
2. A gradient that is greater than 30 mm Mercury with provocation
3. A gradient that is less than 30 mm Mercury at rest and with provocation

• Amyl nitrite inhalation
• Valsalva maneuver
• Premature ventricular contractions (PVCs)
• Isoproterenol infusion
• Dobutamine infusion; but this is not recommended as a diagnostic tool^[20][21]
• Treadmill or exercise stress testing

If dynamic outflow obstruction is present in a patient with HCM, it is usually due to systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. The systolic anterior motion of the mitral valve (SAM) may be due to a subaortic bulge of the septum along with narrowing the left ventricular outflow tract, which taken together cause high-velocity flow. This, in turn, is associated with the Venturi effect which is a local low-pressure zone in the left ventricular outflow tract. This low-pressure zone was thought to suck the mitral valve anteriorly into the septum. More recently, however, SAM onset has been observed to be instead a low-velocity phenomenon. ^{[22] [23]} The role of Venturi forces in the left ventricular outflow tract may be less important than previously thought. While the Venturi effect was thought to cause the abnormality in prior studies, more recent echocardiographic studies indicates that drag, which is more of a pushing force rather than a sucking force like the Venturi effect, maybe the dominant hydrodynamic force acting on the mitral leaflets.^{[22][23][24][25][26][27]}

The videos below show examples of systolic anterior motion of the mitral valve:

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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 pressure will be normal. When the mitral valve leaflet gets pushed into the LVOT, the arterial pulse will momentarily collapse and will later be followed by a second rise in the pulse pressure, as the left ventricular pressure overcomes the increased obstruction caused by the SAM of the mitral valve. 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 pulsus bisferiens or a “spike and dome pattern” to the carotid pulse.

As a result of the drag effect or the Venturi effect, there may be mild to moderate mitral regurgitation in association with hypertrophic cardiomyopathy. Most often the mitral regurgitation jet is directed posteriorly. If the jet is not directed posteriorly then other diagnoses should be considered which include myxomatous degeneration or other anomalies of the mitral valve.

Chronic outflow obstruction and result in the following abnormalities:^[28][29]

• Increased left ventricular wall stress

• Myocardial ischemia

• Myocardial necrosis

• Replacement fibrosis

The presence of outflow obstruction is associated with a twofold increased risk of death and a 4.4 fold increase in the risk of progression to New York Heart Association class III or IV heart failure. ^[30][31] Above a gradient of 30 mm Hg, there was no further increase in the risk of sudden cardiac death or progression of congestive heart failure symptoms.^[32]

There is extensive periarteriolar fibrosis that results in microvascular dysfunction and impairment in coronary flow reserve in patients with hypertrophic obstructive cardiomyopathy.

Compared to normal arterioles on the left, the arterioles from a patient with hyertension (middle) show moderate periarteriolar thickening and fibrosis. Shown on the right is a patient with HCM in which there is even more signficant periarteriolar thickening and fibrosis. This thickening of the wall of the intramyocardial arterioles leads to an increased wall/lumen ratio, subendocardial ischemia and impaired coronary flow reserve.^[33][34] Patients who subsequently died in one series had abnormal coronary flow reserve on PET scanning at baseline indicating that ischemia may play a role, at least in part, in subsequent mortality.

Patients with hypertrophic cardiomyopathy are at risk of arrhythmias and sudden death. Abnormal filling of the left atrium may result in the left atrial dilation which may predispose the patient to atrial fibrillation. The presence of myocardial disarray and myocardial ischemia (due to microvascular dysfunction and episodes of reduced cardiac output) may predispose the patient to ventricular tachycardia, ventricular fibrillation, and sudden cardiac death.

Impaired filling of the left ventricle can lead to left atrial stretch and left atrial dilation. This, in turn, can predispose the patient to the development of atrial fibrillation. The onset of atrial fibrillation can be quite dangerous in these patients as the loss of left atrial kick and the more rapid heart rate can both diminish left ventricular filling which can lead to severe hemodynamic compromise. This hemodynamic compromise can, in turn, be associated with sudden cardiac death.

Ventricular arrhythmias and degeneration into sudden cardiac death may be due to the following:

• Primary arrhythmias
• The presence of myocardial disarray
• The presence of scar or fibrosis
• Hemodynamic instability with diminished stroke volume
• The presence of ischemia

It must be emphasized that atrial arrhythmias (which are commonly detected on ambulatory monitoring) can lead to ischemia and hemodynamic compromise which may, in turn, lead to sudden cardiac death in these patients as well.

Assessment of autonomic function in patients with HCM often reveals abnormal responses of heart rate and blood pressure to exercise in two-thirds, which was associated with a more malignant clinical course, suggesting that autonomic imbalance may also be important in the genesis of sudden cardiac death in these patients.

Individuals with HCM have some degree of left ventricular hypertrophy. In approximately 2/3rds of cases this is asymmetric hypertrophy, involving the interventricular septum, and is known as asymmetric septal hypertrophy (ASH). This is in contrast to the symmetric and concentric hypertrophy seen in aortic stenosis or hypertension.

The degree of ventricular hypertrophy is variable ranging from diffuse involvement of both ventricles to isolated involvement of a portion of one segment of the LV.

Data from two large registries indicate that;

• 55% of cases involve the septum and anterolateral free wall,
• 20% involve the entire septum alone,
• 10% is limited to the nasal septum and 15% are limited to the apical or distal LV (Yamaguchi variant).

Some genetic variants may manifest very little overt LVH but are still associated with an increased risk of sudden cardiac death (SCD).

The left ventricular outflow tract is often small.

The mitral valve maybe elongated and enlarged.

Conditions associated with Hypertrophic cardiomyopathy include:

• [Condition 1]
• [Condition 2]
• [Condition 3]

On histopathologic examination, hypertrophic cardiomyopathy is characterized by both myocardial disarrays and by periarteriolar fibrosis. Myocardial disarray can be associated with aberrant impulse conduction and arrhythmias, and periarteriolar fibrosis can be associated with myocardial ischemia.

In HCM, the normal alignment of muscle cells is disrupted (there is a swirling pattern to the arrangement of the muscle cells), a phenomenon known as myocardial disarray. 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). Histopathologically, the cardiac sarcomere is abnormal resulting in hypertrophy of the left ventricle in the absence of other disorders that could produce the condition such as hypertension, amyloid or aortic stenosis. The presence of myocardial disarray may be associated with abnormalities of electrical conduction in the heart (including electrical reentry loops) which thereby contributes to an increased risk of sudden cardiac death.

Compared to normal arterioles on the left, the arterioles from a patient with hyertension (middle) show moderate periarteriolar thickening and fibrosis. Shown on the right is a patient with HCM in which there is even more signficant periarteriolar thickening and fibrosis. This thickening of the wall of the intramyocardial arterioles leads to an increased wall/lumen ratio, subendocardial ischemia and impaired coronary flow reserve.^[33][34] Patients who subsequently died in one series had abnormal coronary flow reserve on PET scanning at baseline indicating that ischemia may play a role, at least in part, in subsequent mortality.

On gross pathology, asymmetric interventricular wall thickening is characteristic findings of hypertrophic cardiomyopathy. Subaortic stenosis could be evident in many cases. In the Yamaguchi subtype, there is apical hypertrophy.

On microscopic histopathological analysis, myocardial disarray, periarteriolar fibrosis, and hypertrophy are characteristic findings of hypertrophic cardiomyopathy.

Histopathologically, small vessels have hypertrophy of the tunica media. Combined with increased wall tension, decreased vasodilator reserve, and inadequate capillary density, there is a mismatch between blood supply and demand. Over time, it is thought that there is repeated ischemia followed by fibrosis and eventually, dilation and systolic dysfunction (“burned out hypertrophy”).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Cardiomyopathy must be differentiated from athlete heart (which is often confused with HCM on echocardiography), hypertrophy due to hypertension or aortic stenosis; as these have common clinical features, including thickened myocardium on imaging and high QRS voltage on EKGs. On the basis increased LV to aortic gradient, hypertrophic cardiomyopathy must be differentiated from sever volume depletion, subaortic stenosis, and valvular aortic stenosis.

Cardiomyopathy must be differentiated from athlete heart (which is often confused with HCM on echocardiography), hypertrophy due to hypertension or aortic stenosis; as these have common clinical features, including thickened myocardium on imaging and high QRS voltage on EKGs. On the basis increased LV to aortic gradient, hypertrophic cardiomyopathy must be differentiated from sever volume depletion, subaortic stenosis, and valvular aortic stenosis.

On the basis increased LV to aortic gradient, hypertrophic cardiomyopathy must be differentiated from sever volume depletion, subaortic stenosis, and valvular aortic stenosis.

Sever volume depletion:

• These patients may develop hyperdynamic ventricular function in an effort to maintain cardiac output in the setting of normal LV systolic function.
• Here is the sequence of events in this setting:

• Hyperdynamic LV function
• Vigorous blood ejection at a higher velocity than normal
• An increased intracavitary gradient
• This may be mistaken for an increased LVOT gradient.

Subaortic stenosis:

• A congenital abnormality typically caused by a thin membrane of tissue in the LVOT
• Fixed subaortic stenosis can usually be distinguished from HCM and valvular AS by echocardiography or invasive cardiac catheterization.
• There is no systolic anterior motion of the mitral valve, and generally the ventricular wall thickness is normal. Nevertheless, chronic long-standing LV hypertension may finally lead to concentric LVH.
• The aortic valve leaflets are usually normal, but in decades these patients may develop aortic valve damage as well.

Valvular aortic stenosis:

• In addition to potentially causing LVH, narrowing of the aortic valve opening can lead to a significant pressure gradient between the LV and the aorta.
• similar to subaortic stenosis, valvular AS can be distinguished from other pathology by echocardiography or invasive cardiac catheterization.

Cardiomyopathy must be differentiated from athlete heart (which is often confused with HCM on echocardiography), hypertrophy due to hypertension or aortic stenosis; as these have common clinical features, including thickened myocardium on imaging and high QRS voltage on EKGs.

Quite often, HCM can be mistaken for a condition known as athlete’s heart. Both involve the growth of the myocardium, however, the latter generally is not correlated with incidences of SCD. While HCM can be linked to family history, an athlete’s heart arises purely as a function of intense exercise (usually at least an hour a day, every day. Since the body is operating at high training levels, the heart adapts and grows in order to pump blood more efficiently. The stoppage of exercise for three months generally leads to a decrease in wall/septum thickness in those with an athlete’s heart, whereas those with HCM exhibit no decline.

People with an athlete’s heart do not exhibit an abnormally enlarged septum, and the growth of heart muscle at the septum and free ventricular wall is symmetrical. The asymmetrical growth seen in HCM results in a less-dilated left ventricle. This, in turn, leads to a smaller volume of blood leaving the heart with each beat.

Several criteria can be used to distinguish these two entities:

• In athlete’s heart the LVH is symmetric and less than or equal to 12 mm
• Rarely the LV thickness can be 14-16 mm and this makes it difficult to distinguish from HOCM. Athletes who engage in strength training may develop this pattern, athletes who engage in endurance training do not.
• If the degree of thickening is out of proportion to the type and intensity of exercise, this suggests HOCM

• Athleste’s heart is symmetric
• HOCM is more often asymmetric, but may in some cases be symmetric

• HOCM has smaller LV cavitary dimensions

Aortic stenosis must be differentiated from other cardiac or pulmonary causes of dyspnea, weakness, and dizziness. Furthermore, when left ventricular outflow tract obstruction is present, it is critical to identify whether the obstruction is subvalvular, valvular or supravalvular and whether there is hypertrophic cardiomyopathy (HOCM) or not.^[1]

Aortic stenosis can be differentiated from pulmonary causes of dyspnea by the presence of:

• A narrow pulse pressure
• A harsh late-peaking systolic murmur heard best at the right second intercostal space with radiation to the carotid arteries
• A delayed slow-rising carotid upstroke (pulsus parvus et tardus) ^[2]
• Signs of heart failure on examination

While a murmur may be heard in aortic sclerosis, there is no fusion of the commisures and no significant obstruction to antegrade blood flow across the aortic valve. As a result, the S2 is normal in aortic sclerosis and the carotid upstroke is normal (i.e. pulsus parvus et tardus is absent).^[3]

The murmur of aortic stenosis is harsh and best heard at the right second intercostal space while the murmur of mitral regurgitation is blowing, soft and best heard at the apex.^[4]

In HOCM the murmur is dynamic and varies with maneuvers. Moreover, there is a bifid or spoke and dome pattern of the carotid upstroke.^[5]

Aortic insufficiency is more often present with subvalvular aortic stenosis (in 50% to 75% of cases). Symptoms associated with subvalvular aortic stenosis begin earlier in life (in childhood or adolescence) than symptoms associated with valvular aortic stenosis.^[6]

Supravalvular aortic stenosis is an uncommon congenital anomaly caused by a narrowing in the ascending aorta or by the presence of a fibrous diaphragm just above the aortic valve. It presents in early adulthood. Although the aortic valve is not stenotic, doppler shows an increased pressure gradient. 50% of patients with supravalvular aortic stenosis have a characteristically greater pulse and systolic blood pressure in the right carotid and brachial arteries than in the left. The systolic murmur is maximal below the right clavicle and radiates primarily to the right carotid artery. There is not an ejection click nor a diastolic murmur.^[6]

Differentiating hypertrophic cardiomyopathy and valvular aortic stenosis

*A 12 lead EKG is strongly recommended at the time of the initial diagnosis of hypertrophic cardiomyopathy. Common findings on an EKG in these patients include tall R waves, deep Q waves, inverted T waves, ST segment abnormalities and ‘strain pattern’ in the chest leads. The deep Q waves indicate septal hypertrophy and similarly deeply inverted T waves indicate apical hypertrophy.

• Long-standing HTN is the most common cause of LVH

• Most of the LVH due to HTN cases will present beyond adolescence when HCM is most commonly identified.
• The magnitude of hypertrophy seen in hypertension, however, rarely leads to wall thicknesses in excess of 1.5 cm.
• Hypertension is usually suspected in persons with an extended history of elevated blood pressures (10 or more years), particularly in those with other evidence of end-organ damage due to hypertension (eg, retinopathy, nephropathy).

(X-linked deficiency of the lysosomal enzyme alphagalactosidase)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ogheneochuko Ajari, MB.BS, MS [2] Soroush Seifirad, M.D.[3]

Hypertrophic cardiomyopathy is a condition that is most often passed down through families (inherited). It is thought to result from gene mutations that control heart muscle growth. Genes involved in the pathogenesis of hypertrophic cardiomyopathy include MYH7, TNNT2, TPM1. Nevertheless, a number of chronic medical conditions might be contributed to hypertrophic cardiomyopathy development, among them are thyroid disease, diabetes, and obesity, and hypertension.

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

• Familial
• Gene mutation
• Hypertension
• Thyroid disease
• Diabetes
• Obesity

• Aging
• Atrial myxoma^[1]
• Cardiofaciocutaneous syndrome
• Congenital generalized lipodystrophy type 2
• Costello syndrome ^[2]
• Cytochrome c oxidase deficiency
• Diabetes mellitus
• Dihydrolipoamide dehydrogenase deficiency
• Fabry’s disease^[3]
• Familial
• Friedreich’s ataxia^[4]
• Gene mutation
• Glycogenosis type 2
• Hereditary spherocytosis
• Hypertension
• Hypertrichotic osteochondrodysplasia
• Hypertrophic obstructive cardiomyopathy
• Idiopathic
• Long-chain acyl-CoA dehydrogenase deficiency
• Malonyl-CoA decarboxylase deficiency
• MELAS
• Multiple lentigines syndrome
• Muscle glycogen synthase deficiency
• Myotonic dystrophy^[5]
• Noonan syndrome^[6]
• Sarcomeric protein mutations
• Subendocardial ischemia
• Thyroid disease
• Very long-chain acyl-CoA dehydrogenase deficiency^[7]
• Yunis-Varon syndrome

Hypertrophic cardiomyopathy is transmitted in an autosomal dominant pattern.

Genes involved in the pathogenesis of hypertrophic cardiomyopathy include:

• MYH7
• TNNT2
• TPM1

The development of Hypertrophic cardiomyopathy is the result of multiple genetic mutations such as:

• Beta-myosin heavy chain
• Myosin binding protein C
• Cardiac troponin T

HCM is the most common genetically transmitted cardiovascular disease. 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.  Penetrance of HCM is incomplete, variable and time or age-related. The disease may be sporadic but affected family members are discovered in 13% of cases. More than 200 mutations involving at least 10 chromosomes encoding structural proteins of the myocyte have been discovered. These mutations have varying degrees of penetrance and even the same mutation may have variable expression, implying the superimposed effects of other genes or environmental influences. Children of a patient with HCM have a 50% chance of inheriting the trait.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Prevalence rates have been reported between 1:500 (0.2%) and 1:3,000 (0.03%) because of variations in study designs and cohort characteristics including different age groups and ethnicity. According to the CARDIA (Coronary Artery Risk Development in Young Adults) cohort study that used standard echocardiography in 4,111 unrelated people 23 to 35 years of age, HCM prevalence is reported as 1 in 500 persons (0.2%). Nevertheless, lower prevalence has been reported in some European countries such as Germany (0.07%). Patients of all age groups may develop hypertrophic cardiomyopathy. Prevalence increased with advancing age and showed a constant yearly rise but sudden death is more prevalent in young patients, particularly athletes. The case-fatality rate is 6 per 10,000 per year in young people without symptoms of hypertrophic cardiomyopathy but in syptomatic patients a case-fatality rate is 420 and 110 deaths per 10,000 per year in tertiary referral centers and general hospital clinics respectively. Hypertrophic cardiomyopathy affects men and women equally. However, despite more frequent outflow obstruction, women with HCM are underrecognized and referred to centers later than men, often with more advanced heart failure. Greater awareness of HCM in women should lead to earlier diagnosis and treatment, with implications for improved quality of life. HCM is less prevalent in African Americans, but they are more pron to early presentation, developing heart failure, and sudden death is more prevalent due to less awareness and screening in this population.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Prevalence rates have been reported between 1:500 (0.2%) and 1:3,000 (0.03%) because of variations in study designs and cohort characteristics including different age groups and ethnicity. According to the CARDIA (Coronary Artery Risk Development in Young Adults) cohort study that used standard echocardiography in 4,111 unrelated people 23 to 35 years of age, HCM prevalence is reported as 1 in 500 persons (0.2%).^[1] Nevertheless, lower prevalence has been reported in some European countries such as Germany (0.07%). ^[2]A recent analysis of U.S. claims data reported a prevalence of clinically diagnosed HCM in approximately 1:3,000 (0.03%)^[3] According to Semsarian et al. “For the past 20 years, most data have supported the occurrence of HCM at about 1 in 500. However, the authors have interrogated a number of relevant advances in cardiovascular medicine, including widespread fee-for-service genetic testing, population genetic studies, and contemporary diagnostic imaging, as well as a greater index of suspicion and recognition for both the clinically expressed disease and the gene-positive– phenotype-negative subset (at risk for developing the disease). Accounting for the potential impact of these initiatives on disease occurrence, the authors have revisited the prevalence of HCM in the general population.”^[4]

• The incidence/prevalence of Hypertrophic cardiomyopathy is approximately [number range] per 100,000 individuals worldwide.
• In [year], the incidence/prevalence of Hypertrophic cardiomyopathy was estimated to be [number range] cases per 100,000 individuals worldwide.

• The prevalence of hypertrophic cardiomyopathy is approximately 200 per 100,000 individuals worldwide. Nevertheless recent studies suggested a higher prevalence. ^[4]

• The case-fatality rate/mortality rate of is different in asymptomatic vs symptomatic patients.
• The case-fatality rate is 6 per 10,000 per year in young people without symptoms of hypertrophic cardiomyopathy but in syptomatic patients a case-fatality rate is 420 and 110 deaths per 10,000 per year in tertiary referral centers and general hospital clinics respectively.
• Although it is quite prevalent, hypertrophic cardiomyopathy rarely causes death; the case-fatality rate is about 6 per 10,000 per year in young people without symptoms of hypertrophic cardiomyopathy.^[5]
• Current risk estimates from the study of patients in tertiary referral centers or general hospital clinics are not applicable to asymptomatic people in the general population.^[6]

• Patients of all age groups may develop hypertrophic cardiomyopathy.
• Patients can be diagnosed at any age, from birth to age 80 and beyond.
• Children and adolescents with the condition usually come to attention when a family screening is performed after an adult in the family is found to be affected or at the presence of a heart murmur that is evaluated more closely.
• Approximately 50% of adults with the condition present with symptoms, the average age of diagnosis within the HCMA database is 39 years.
• Prevalence increased with advancing age and showed a constant yearly rise.
• But sudden death is more prevalent in young patients, particularly athletes.
• Hypertrophic cardiomyopathy can cause heart-related sudden death in people of all ages, but the condition most often causes sudden cardiac death in people under the age of 30.

• For years, HCM was considered an uncommon condition among the African American population. Maron et al, in a multicenter analysis of clinically diagnosed HCM patients noted only 8% of the study population was black. In Movahed et al study, African Americans constitute only 9% of the population. However, in the light of several premature cardiovascular deaths among African American athletes, Maron et al, in an autopsy analysis of young athletes surprisingly noted HCM was 7 times more commonly identified in African Americans for the first time at autopsy compared to when clinically identified in African American population.^[7]
• HCM-related sudden death is more prevalent in black male athletes.^[8]Many HCM cases go unrecognized in the African American community, underscoring the need for enhanced clinical recognition of HCM to create the opportunity for preventive measures to be employed in high-risk patients with this complex disease.
• According to Sheikh et al who studied 425 patients in the UK, there are differences in presenting features including the prevalence of hypertension and an abnormal ECG in black and white patients with HCM. Apical and concentric hypertrophy is more common in black patients and may have implications for appropriate diagnosis, especially in those with concurrent hypertension. Overall freedom from adverse events is similar.^[9]

• Sorensen et al compared 76 blacks for clinical presentation, electrocardiogram, exercise capacity, left ventricular morphology, and hemodynamics by echocardiography to 365 whites. They concluded that “blacks have an HC phenotype characterized by a lower prevalence of the well-recognized echocardiographic features of HC such as the systolic anterior movement of the mitral valve and left ventricular outflow tract obstruction and display worse exercise capacity.”^[10]
• The Sarcomeric Human Cardiomyopathy Registry (1989 – 2018)

• Lauren A. Eberly, M.D., identified 2,467 patients with hypertrophic cardiomyopathy (8.3 percent black; 91.7 percent white). Black patients were younger at the time of diagnosis (mean age, 36.5 versus 41.9 years), had a higher prevalence of New York Heart Association (NYHA) class III or IV heart failure at presentation (22.6 versus 15.8 percent), had lower rates of genetic testing (54.1 versus 62.1 percent) and were less likely to have sarcomeric mutations identified by genetic testing (26.1 versus 40.5 percent) compared with white patients. There were no racial differences noted in implantation of implantable cardioverter-defibrillators, but the invasive septal reduction was less common among black patients (14.6 versus 23 percent). Black patients had less incident atrial fibrillation (35 [17.1 percent] versus 608 [26.9 percent]). There was an association between black race and increased development of NYHA class III or IV heart failure (hazard ratio, 1.45).^[11]

• The United States National Registry

• Within this large forensic registry of competitive athletes, cardiovascular sudden deaths due to genetic and/or congenital heart diseases were uncommon in females and more common in African Americans/other minorities than in whites. Hypertrophic cardiomyopathy is an under-appreciated cause of sudden death in male minority athletes.^[12]

Germany

• Prevalence of clinically diagnosed HCM in Germany is lower than in systematic population studies based on the echocardiographic diagnosis.

• Hypertrophic cardiomyopathy affects men and women equally.
• Survival was not less favorable in women with HCM.
• Contemporary treatments including surgical myectomy to reverse heart failure and defibrillators to prevent sudden death, were effective in both sexes contributing to low mortality.
• However, despite more frequent outflow obstruction, women with HCM are underrecognized and referred to centers later than men, often with more advanced heart failure. Greater awareness of HCM in women should lead to earlier diagnosis and treatment, with implications for improved quality of life.^[13][14]

• The majority of Hypertrophic cardiomyopathy cases are reported in [geographical region].

• Hypertrophic cardiomyopathy is a common/rare disease that tends to affect [patient population 1] and [patient population 2].

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Obstructive hypertrophic cardiomyopathy (HCOM) is known as a familial genetic disorder. The most potent risk factor in the development of hypertrophic cardiomyopathy aregenetic mutations in Beta-myosin heavy chain, Myosin binding protein C, and Cardiac troponin T. Genes involved in the pathogenesis of hypertrophic cardiomyopathy include but not limited to MYH7, TNNT2, TPM1. However, hypertension, thyroid disease, diabetes, and obesity also play a role in non obstructive forms of hypertrophic cardiomyopathy. This is in response to chronic effects of abnormal pressure and volumes on the myocardium and is different from apical hypertrophy (Yamaguchi syndrome).

Obstructive hypertrophic cardiomyopathy (HCOM) is known as a familial genetic disorder. The most potent risk factor in the development of hypertrophic cardiomyopathy aregenetic mutations in Beta-myosin heavy chain, Myosin binding protein C, and Cardiac troponin T. Genes involved in the pathogenesis of hypertrophic cardiomyopathy include but not limited to MYH7, TNNT2, TPM1. However, hypertension, thyroid disease, diabetes, and obesity also play a role in non obstructive forms of hypertrophic cardiomyopathy. This is in response to chronic effects of abnormal pressure and volumes on the myocardium and is different from apical hypertrophy (Yamaguchi syndrome).

• Common risk factors in the development of hypertrophic cardiomyopathy are genetic mutations in Beta-myosin heavy chain, Myosin binding protein C, and Cardiac troponin T.
• Genes involved in the pathogenesis of hypertrophic cardiomyopathy include:
  • MYH7
  • TNNT2
  • TPM1

• Less common risk factors in the development of non obstructive/non genetic hypertrophic cardiomyopathy include:
  • Hypertension
  • Thyroid disease
  • Diabetes
  • Obesity

Patients with hypertrophic cardiomyopathy are increased risk of sudden cardiac death. Identification of those patients at an increased risk can facilitate early treatment with an automatic implantable cardiac defibrillator.

Risk factors for sudden death in individuals with HCM include:^[1]

• 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
• A hypotensive response to exercise
• Recurrent syncope (especially in children)
• Bradyarrhythmias (slow rhythms of the heart).

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2] Soroush Seifirad, M.D.[3]

Genetic testing is the diagnostic study of choice to definitively diagnose hypertrophic cardiomyopathy. While definitive, these techniques can be expensive and can be difficult to access. If the mutation has already been identified in other family members, it is fairly efficient to test for that isolated mutation. Once HCM has been identified in a family, immediate testing of all family members will help to identify those at risk.

Absent the availability of genetic testing, clinical screening should be conducted using the history, physical exam, the electrocardiogram and the echocardiogram in adolescent patients aged 12 to 18 who are first degree relatives of patients with a confirmed diagnosis of hypertrophic cardiomyopathy. Because HCM can have a delayed age of onset, individuals over the age of 18 with an affected first degree relative should have screening every 5 years. Unless the child is engaged in extremely competitive sports or has an aggressive family history of HCM with premature death, screening is generally not recommended in children under the age of 12.

Screening for hypertrophic cardiomyopathy(HCM) is a controversial subject in the medical community, as HCM is the leading cause of sudden death in athletes.

The AHA/ACC guidelines recommend that a family history should be obtained in athletes to ascertain if there is a history of sudden death or if HCM is present in any family members.

If the family history is positive, then a physical examination and echocardiography should be performed.

• In Italy, all competitive athletes are required to undergo pre-participation screening for the presence of HCM.

• This screening consists of:

• A 12-lead ECG
• A general and cardiovascular physical examination, including blood pressure measurements
• A family history

• Over 3 million competitive athletes are evaluated each year, and athletes judged to be free of cardiovascular disease receive a certificate enabling them to participate in competitive athletics.

• In a study done in Italy over a 9-year period (1990-1998), 41 of the 4450 athletes screened on echocardiography showed LV hypertrophy, with an increased wall thicknesses. Only four athletes demonstrated a maximal LV wall thickness of 13 mm or more. Thus, the yield of echocardiographic screening appears to be low.

These patients are re-evaluated every 12 to 18 months.

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ^[29][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Lakshmi Gopalakrishnan, M.B.B.S. [2] Soroush Seifirad, M.D.[3] Laith Adnan Allaham, M.D.[4]

The natural history of hypertrophic cardiomyopathy is quite variable. Signs and symptoms range from none, to atrial fibrillation, heart failure, embolic stroke and sudden cardiac death. Signs and symptoms are quite variable from individual to individual but are also quite variable within a given family (all of whom carry the same mutation). The disease is quite variable in the timing of its appearance and may appear anywhere from infancy to late in adult life. About 25% of HCM patients achieve normal longevity. The myosin-binding proteins C genetic variant carries a good prognosis. The presence of ventricular fibrillation/ ventricular tachycardia carries the poorest prognosis. The severity of the outflow gradient is also related to prognosis. Athletes should be screened for HOCM based upon a family history of sudden cardiac death and a murmur on physical examination. Electrocardiograms and echocardiograms are not cost-effective screening tools in this population with a low pre-test probability of disease.

The natural history of hypertrophic cardiomyopathy is quite variable. Signs and symptoms range from none, to atrial fibrillation, heart failure, embolic stroke and sudden cardiac death.^{[1][2][3][4][5]} Signs and symptoms are quite variable from individual to individual but are also quite variable within a given family (all of whom carry the same mutation). The disease is quite variable in the timing of its appearance and may appear anywhere from infancy to late in adult life. About 25% of HCM patients achieve normal longevity.^[6][7][8][9]The myosin binding proteins C genetic variant carries a good prognosis. The presence of VT / VF carries the poorest prognosis. The severity of the outflow gradient is also related to prognosis. Athletes should be screened for HOCM based upon a family history of sudden cardiac death and a murmur on physical examination. Electrocardiograms and echocardiograms are not cost-effective screening tools in this population with a low pre-test probability of disease.

Left ventricular hypertrophy may be absent in childhood. It may then appear following the rapid growth of adolescence and may first appear at age 17 to 18.^[10][11][12]

The incidence of sudden cardiac death (SCD) in patients with HCM is 2 to 4 percent per year in adults, and a 4 to 6 percent per year in children and adolescents.^[13]

Among end stage patients with a left ventricular ejection fraction < 50%, the risk of SCD over 5 years may be as high as 47%. In this population, syncope has been identified as an independent correlate of sudden cardiac death (hazard ratio = 6.15; 95% confidence interval, 2.40-15.75; P < .001).^[14]

A review of 78 patients with HCM who died suddenly or survived a cardiac arrest episode showed that 71 percent were younger than 30 years of age, 54 percent were without functional limitation, and 61 percent were performing a sedentary or minimal physical activity at the time of the cardiac arrest.

There are few predictors of SCD in patients with HCM.

• Onset of symptoms in childhood. ^[15][16]
• A clinical history of spontaneous, sustained monomorphic ventricular tachycardia (VT) or sudden death in family members.
• History of impaired consciousness
• Syncope
• Atrial arrhythmias
• Development of systolic dysfunction
• Non-sustained ventricular tachycardia (NSVT) in patients with symptoms
• Left ventricular wall thickness >30 mm. A recent report of 480 patients showed that left ventricular wall thickness was useful in identifying patients at high risk for sudden cardiac death. However, sudden cardiac death can occur in children and adolescents in the absence of left ventricular hypertrophy as well.

Survivors of SCD have a poor prognosis. Event free survival at 1, 5, and 10 years was 83, 65, and 53 percent respectively.

^[19][20]

2011 ACCF/AHA Guideline for the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ^[19][20]

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