Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy ("HCM") is a disease of the myocardium (the muscle of the heart) in which a portion of the myocardium is hypertrophied (thickened) without any obvious cause.[1][2][3][4][5][6] It is perhaps best known as a leading cause of sudden cardiac death in young athletes.[7] 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.[citation needed]
HCM is frequently asymptomatic until sudden cardiac death, and for this reason some suggest routinely screening certain populations for this disease.[8]
A cardiomyopathy is a primary disease that affects the muscle of the heart. With HCM, the sarcomeres (contractile elements) in the heart 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 genes 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
The clinical course of HCM is variable. Many patients are asymptomatic or mildly symptomatic. The symptoms 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.[9] 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.
Traditional risk factors for sudden death in individuals with HCM include unexplained syncope, family history of SCD, marked left ventricular hypertrophy (≥ 30 mm), ventricular tachycardia, and a decrease or subnormal (< 20mmHg) increase in systolic blood pressure on exercise testing.[10] Non-traditional risk factors include specific mutations in the genes encoding for troponin T and myosin and bradyarrhythmias (slow rhythms of the heart).[11]
== Genetics==
Gene 	Locus 	Type
MYH7 	14q12 	CMH1 (192600)
TNNT2 	1q32 	CMH2 (115195)
TPM1 	15q22.1 	CMH3 (115196)
MYBPC3	11p11.2 	CMH4 (115197)
? 	? 	CMH5
PRKAG2	7q36 	CMH6 (600858)
TNNI3 	19q13.4 	CMH7
MYL3 	3p 	CMH8 (608751)
TTN 	2q24.3 	CMH9
MYL2 	12q23-q24	CMH10
ACTC1 	15q14 	CMH11 (612098)
CSRP3 	11p15.1 	CMH12 (612124)
Familial 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.
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 [12] .[13]
Some mutations (troponin) have much more malignant potential compared to others (β myosin heavy chain). For example, troponin T mutations are associated with a 50% mortality before the age of 40.
== Pathophysiology==
Individuals with HCM have some degree of left ventricular hypertrophy. Usually this is an asymmetric hypertrophy, involving the inter-ventricular septum, and is known as asymmetric septal hypertrophy.[14] 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 as much as 70% of patients however obstruction can be provoked under certain conditions. This is known as dynamic outflow obstruction, because the degree of obstruction is variable and is dependent on the loading conditions (ventricular filling and arterial blood pressure) and the contactility state of the left venticle.
Myocardial hypertrophy and extracellular fibrosis predispose to increased left venticular stiffness which in concert with compromised cellular energetics and abnormal calcium handling lead to diastolic dysfunction manifested as dyspnea and exercise intolerance.
The altered structure of the coronary vessels and increased diastolic pressure (reduced blood supply) together with the hypertrophy and the outflow tract obstruction (increased demand) cause myocardial ischemia that is manifested as angina and may be responsible for the triggering of venticular arrhythmias.
In about 30% of patients there are abnormal vascular responses and inability to increase systolic blood pressure during exercise. This is attributed to exaggerated cardiac inhibitory reflexes initiated by increased myocardial wall stress and to elevated levels of vasodilating substances (natriuretic peptides).
=== Dynamic outflow obstruction===
 	Systolic anterior motion of the mitral valve Echocardiogram demonstrating systolic anterior motion of the anterior leaflet of the mitral valve----
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Dynamic outflow obstruction (when present in HCM) is usually due to systolic anterior motion of the anterior leaflet of the mitral valve. Systolic anterior motion of the mitral valve (SAM) was initially thought to be due to the septal subaortic bulge, narrowing the outflow tract, causing high velocity flow and a Venturi effect—a local underpressure in the outflow tract. Low pressure was thought to suck the mitral valve anteriorly into the septum. But SAM onset is observed to be a low velocity phenomenon: SAM begins at velocities no different from those measured in normals. [15] [16] 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. [15] [16] [17] [18] [19] [20] In obstructive HCM the mitral leaflets are often large [21] and are anteriorly positioned in the LV cavity [15] [22] due to anteriorly positioned papillary muscles[15] that at surgery are often "agglutinated" onto the LV anterior wall by abnormal attachments. [19] [20]
The mid-septal bulge aggravates the malposition of the valve and redirects outflow so that it comes from a lateral and posterior direction.[17] 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 [15] [16] [17] [18] There is a crucial overlap between the inflow and outflow portions of the left ventricle. [23] 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.[17] 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. [15] [16] [17] [18] SAM may be considered anteriorly directed mitral prolapse [16] [17] [18] 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.[24]
==[edit] Screening==
Main article: Hypertrophic cardiomyopathy screeningAlthough HCM may be asymptomatic, affected individuals may present with symptoms ranging from mild to critical heart failure and sudden cardiac death at any point from early childhood to seniority.[25][26] HCM is the leading cause of sudden cardiac death in young athletes in the United States, and the most common genetic cardiovascular disorder.[27] One study found that the incidence of sudden cardiac death in young competitive athletes declined in the Veneto region of Italy by 89% since introduction of routine Hypertrophic Cardiomyopathy Screening of athletes.[28] As of 2010, however, studies have shown that the incidence of sudden cardiac death, among all HCM patients, has declined to one percent, or less.[29] HCM can be detected with an echocardiogram with 80%+ accuracy,[citation needed] which can be preceded by screening with an electrocardiogram (ECG) to test for heart abnormalities. Cardiac magnetic resonance imaging (CMR), considered the gold standard for determining the physical properties of the left ventricular wall, can serve as an alterative screening tool when an echocardiogram provides inconclusive results.[30] For example, the identification of segmental lateral ventricular hypertrophy cannot be accomplished with echocardiography alone. Also, left ventricular hypertrophy may be absent in children under thirteen years of age. This undermines the results of pre-adolescents’ echocardiograms.[26] Researchers, however, have studied asymptomatic carriers of a HCM-causing mutation through the use of CMR and have been able to identify crypts in the interventricular septal tissue in these patients. It has been proposed that the formation of these crypts is an indication of myocyte disarray and altered vessel walls that may later result in the clinical expression of HCM.[30] Lastly, giving warning of heart abnormalities in only 3% of patients before sudden cardiac death, the gathering of family history and physical examination alone are ineffective.[8] A possible explanation for this is that the gathering of family history only focuses on whether sudden death occurred or not. It fails to acknowledge the age at which relatives suffered sudden cardiac death, as well as the frequency of the cardiac events. Furthermore, given the several factors necessary to be considered at risk for sudden cardiac death, and that no factor is more important than another, there exists ambiguity regarding when to implement special treatment.[31]
=== United States===
There are several potential challenges associated with routine screening for HCM in the United States.[32] First, the U.S. athlete population of 15 million is almost twice as large as Italy's estimated athlete population.[32] Second, these events are extremely rare in the U.S., with fewer than 100 deaths due to HCM in competitive athletes per year,[33] or about 1 death per 220,000 athletes.[34] Lastly, genetic testing would provide a definitive diagnosis; however, due to the numerous HCM-causing mutations, this method of screening is complex, and is not cost-effective.[2] Therefore, genetic testing in the United States is limited to individuals which exhibit clear symptoms of HCM. This ensures that the test is not wasted on detecting other causes of ventricular hypertrophy (due to its low sensitivity), and that family members of the individual are educated on the potential risk of being carriers of the mutant gene(s).[35]
In the United States such screening is not routine and the American Heart Association has "consistently opposed" routine screening.[8]
=== Canada===
Canadian genetic testing guidelines and recommendations for individuals diagnosed with HCM are as follows.
*The main purpose genetic testing is for screening family members.[36]
**According to the results, at-risk relatives may be encouraged to undergo or avoid extensive testing.[36]
*Genetic testing is not meant for confirming a diagnosis.[36]
**If the diagnosed individual has no relatives that are at risk, then genetic testing is not required.[36]
*Genetic testing is not intended for risk assessment or treatment decisions.[36]
**Evidence only supports clinical testing in predicting the progression and risk of developing complications of HCM.[36]
For individuals suspected of having HCM
*Genetic testing is not recommended for determining other causes of left ventricular hypertrophy (such as athlete's heart, hypertension, and cardiac amyloidosis).[36]
**HCM may be differentiated from other hypertrophy-causing conditions using clinical history and clinical testing.[36]
== Diagnosis==
A diagnosis 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 (although not primarily used for diagnosis)[36] findings and if there is any family history of HCM or unexplained sudden death in otherwise healthy individuals.
===[edit] Obstructive and non-obstructive===
Depending on whether the distortion of normal heart anatomy causes an obstruction of the outflow of blood from the left ventricle of the heart, HCM can be defined as obstructive or non-obstructive.
*The obstructive variant of HCM, hypertrophic obstructive cardiomyopathy (HOCM) has also historically been known as idiopathic hypertrophic subaortic stenosis (IHSS) and asymmetric septal hypertrophy (ASH).
*Another, non-obstructive variant of HCM is apical hypertrophic cardiomyopathy,[37] also called Yamaguchi Syndrome or Yamaguchi Hypertrophy, first described in individuals of Japanese descent.
===Physical examination===
Differentiating hypertrophic cardiomyopathy and valvular aortic stenosis
 	Aortic stenosis 	Hypertrophic cardiomyopathy
Echocardiography 	Echocardiography 	Echocardiography
Aortic valve calcification	Common 	No
Dilated ascending aorta 	Common 	Rare
Ventricular hypertrophy 	Concentric LVH 	Asymmetric, often involving the septum
Physical examination 	Physical examination 	Physical examination
Murmur of AI 	Common 	No
Pulse pressure after PVC 	Increased 	Decreased
Valsalva maneuver 	Decreased intensity of murmur	Increased intensity of murmur
Carotid pulsation 	Normal or tardus et parvus 	Brisk, jerky, or bisferiens pulse (a collapse of the pulse followed by a secondary rise)
The physical findings of HCM are associated with the dynamic outflow obstruction that is often present with this disease.
Upon auscultation, the heart 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 abruptly or the strain phase of a Valsalva maneuver). Administration of amyl nitrite will also accentuate the murmur by decreasing venous return to the heart. 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 contractions (PVCs), the change in the carotid pulse intensity in the beat after the PVC can help differentiate HCM from aortic stenosis. In individuals with HCM, the pulse pressure will decrease in the beat after the PVC, while in aortic stenosis, the pulse pressure will increase. However, the murmur intensity increases with both Aortic Stenosis and HCM post-PVC.
===[edit] Cardiac catheterizationUpon cardiac catheterization, catheters can be placed in the left ventricle and the ascending aorta, to measure the pressure difference between these structures. In normal individuals, during ventricular systole, the pressure in the ascending aorta and the left ventricle will equalize, and the aortic valve is open. In individuals with aortic stenosis or with HCM with an outflow tract gradient, there will be a pressure gradient (difference) between the left ventricle and the aorta, with the left ventricular pressure higher than the aortic pressure. This gradient represents the degree of obstruction that has to be overcome in order to eject blood from the left ventricle.===
The Brockenbrough–Braunwald–Morrow sign is observed in individuals with HCM with outflow tract gradient. This sign can be used to differentiate HCM from aortic stenosis. In individuals with aortic stenosis, after a premature ventricular contraction (PVC), the following ventricular contraction will be more forceful, and the pressure generated in the left ventricle will be higher. Because of the fixed obstruction that the stenotic aortic valve represents, the post-PVC ascending aortic pressure will increase as well. In individuals with HCM, however, the degree of obstruction will increase more than the force of contraction will increase in the post-PVC beat. The result of this is that the left ventricular pressure increases and the ascending aortic pressure decreases, with an increase in the LVOT gradient.
While the Brockenbrough–Braunwald–Morrow sign is most dramatically demonstrated using simultaneous intra-cardiac and intra-aortic catheters, it can be seen on routine physical examination as a decrease in the pulse pressure in the post-PVC beat in individuals with HCM.
==[edit] Treatment==
The management of patients with HCM encompasses (1) activity restriction with avoidance of volume depletion, (2) control of symptoms, (3) prevention of sudden death, and (4) screening of relatives.[38][39] In patients with obstructive HC, measures to control symptoms are directed at lessening the obstruction to left ventricular outflow with drugs or mechanical measures. Pharmacologic agents useful for management of symptoms in HOCM include beta blockers, nondihydropyridine calcium channel blockers,12 and disopyramide. Mechanical procedures for HOCM include septal myectomy, ASA, and pacing with short atrioventricular delay.[39] The Massachusetts General Hospital "MGH" algorithm for the management of symptoms of patients with obstructive hypertrophic cardiomyopathy "HOCM" is one accepted treatment strategy (Algorithm for Management of Symptoms in Hypertrophic Cardiomyopathy).[38]
The likelihood of drug therapy controlling symptoms among patients with HOCM and the predictors of failure of medical treatmemt was assessed in an analysis by Rothman et al.[40] In this study, the authors evaluated the efficacy of an algorithm for the management of symptoms and the predictors of failed conservative therapy in 249 consecutive symptomatic patients with HOCM referred to the Massachusetts General Hospital. The investigators identified considerable practice variation in the extent to which conservative therapy was optimized prior to referral for more aggressive procedures. Among the study cohort, symptoms resolved with addition of or increase in dosage of a beta blocker, a calcium channel blocker, or disopyramide in 16%, 10%, and 10% of patients, respectively. Pacing with short atrioventricular delay controlled symptoms in 4 of 9 patients. In 63% of patients, conservative measures failed to control symptoms. Multivariate predictors of failure of conservative therapy were presence of NYHA Class III or IV symptoms (HR 2.0, 95% CI 1.4-2.9; p=0.001) and greater septal wall thickness (HR 1.06, 95% CI 1.02-1.10; p=0.003) at presentation. At the time of presentation, 93 patients (37%) were already on optimal therapy and were referred for SRT. Of the remaining 156 patients who did not require immediate SRT, 93 (60%) were free from a recommendation for SRT at the end of the follow up period. The authors concluded that among symptomatic patients with HOCM, conservative therapy is successful in more than a third of patients, obviating the need for SRT in these patients and recommend that clinicians in programs offering mechanical therapies for HOCM should first optimize drug therapies.
A high risk of suffering sudden cardiac death may be indicated by a ventricular wall thickness greater than 30mm, unexplained syncope, family history of sudden cardiac death, abnormal blood pressures after exercise, and occurrence of cardiac arrest.[31] Other less well-known factors may be identified in HCM patients.[31] In those patients deemed to be at high risk, an implantable cardioverter defibrillator (ICD) may be implanted; devices have been implanted in as many as 15% of patients at HCM centers[citation needed]. 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.[41] 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 (metoprolol, atenolol, bisoprolol, propranolol).[42] If symptoms and gradient persist, disopyramide may be added to the beta-blocker.[43] Alternately a calcium channel blocker such as verapamil may be substituted for a beta blocker.
===[edit] Surgical myectomy===
Surgical septal myectomy is an open heart operation done to relieve symptoms in patients who remain severely symptomatic despite medical therapy.[2][3][5][6][43][44] 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%, as well as 85% success rate.[25] It involves a median sternotomy (general anesthesia, opening the chest, and cardiopulmonary bypass) and removing a portion of the interventricular septum.[2] 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.[3][45] 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.[3][19][20][46] In selected patients with particularly large redundant mitral valves, anterior leaflet plication may be added to complete separation of the mitral valve and outflow.[46][47] Complications of septal myectomy surgery include possible death, arrhythmias, infection,incessant bleeding, septal perforation/defect, stroke.[25]
===[edit] Alcohol septal ablation===
Alcohol septal ablation, introduced by Ulrich Sigwart in 1994, is a percutaneous technique that involves injection of alcohol into one or more septal branches of the left anterior descending artery. This is a technique with results similar to the surgical septal myectomy procedure but is less invasive, since it 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.[2][5][48]
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.[49]
===[edit] Ventricular pacing===
The use of a pacemaker has been advocated in a subset of individuals, in order to cause asynchronous contraction of the left ventricle. Since the pacemaker activates the interventricular septum before the left ventricular free wall, the gradient across the left ventricular outflow tract may decrease. This form of treatment has been shown to provide less relief of symptoms and less of a reduction in the left ventricular outflow tract gradient when compared to surgical myectomy.[50] Technological advancements have also lead to the development of a dual-chamber pacemaker, which is only turned on when needed (in contrast to a regular pacemaker which provides a constant stimulus). Although the dual-chamber pacemaker has shown to decrease ventricular outflow tract obstruction, experimental trials have only found few individuals with improved symptoms.[31] Unfortunately, researchers suspect that these reports of "improved" symptoms are due to a placebo effect.[25]
*Procedure includes an incision on the anterolateral area below the clavicle. Two leads are then inserted; one into the right atria and the other into the right ventricular apex via the subclavian veins. Once in place, they are secured and attached to the generator which will remain inside the patient's fascia, anterior to the pectoral muscle.[25] Complications of this procedure include infection, electrical lead and generator malfunction which will require replacement.[25]
===[edit] Cardiac transplantation===
In cases that are refractory to all other forms of treatment, cardiac transplantation is an option. It is also the only treatment available for end-stage heart failure.[31] However, transplantation must occur before the onset of symptoms such as pulmonary vessel hypertension, kidney malfunction, and thromboembolism in order for it to be successful. Studies have indicated a seven year survival rate in 94% in patients after transplantation.[31]
==[edit] Society and culture==
===[edit] Notable cases===
After the death of Marc-Vivien Foé of Cameroon during a 2003 FIFA Confederations Cup match, his autopsy revealed hypertrophic cardiomyopathy.[51] Miklós "Miki" Fehér, a Hungarian football player who died during a match on January 25, 2004, also suffered from HCM.[52][53]
On December 10, 2008, NBA player Cuttino Mobley announced his retirement due to worsening HCM.[54] 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.[55]
Other noted athletes believed or suspected to have died from HCM include NFL players Thomas Herrion,[56] Mitch Frerotte,[57] Gaines Adams,[58][59] and Derrick Faison;[60] NBA players Reggie Lewis,[61][62] Jason Collier,[59] and Kevin Duckworth;[63] NHL player Sergei Zholtok;[56] baseball pitcher Joe Kennedy;[56] long distance runner Ryan Shay;[64] Loyola Marymount basketball star Hank Gathers;[65] Loyola Marymount soccer player David Kucera;[66] Kansas State football player Anthony Bates;[67] Russian ice hockey star Alexei Cherepanov;[68] and American strongman Jesse Marunde.[69]
The Ontario Hockey League's Mickey Renaud Captain's Trophy honors former Windsor Spitfires captain Mickey Renaud, who died of HCM at age 19.[70]
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.[71]
Internet personality Ben Breedlove of Austin, Texas died on December 25, 2011, from HCM at age 18.[72][73]
==[edit] In children==
Hypertrophic cardiomyopathy (HCM) is one of the most uncommon cardiac malformations encountered in pediatric cardiology. This attributed largely to the phenotypes is usually absent, incomplete, or delayed into adulthood. Most of current information pertaining HCM arises from studies in adult populations, and the implication of these observations for pediatric population is often uncertain.[74] Nonetheless, recent studies in pediatric cardiology have revealed that HCM accounts for 42% of childhood cardiomyopathies with an incidence report of 0.47/100,000 in children.[75] Further, in asymptomatic cases, sudden death is considered one of the most feared complications associated with the disease in select pediatric population. Consequently, the recommended practice is to start screening children of affected individuals throughout childhood to detect cardiac abnormalities at an early stage in hope to prevent further complication of the disease.[76]
Generally, the diagnosis of HCM in a pediatric population is made during assessment for murmur, congestive heart failure, physical exhaustion, and genetic testing of children of affected individuals.[74] Specifically, echocardiogram (ECHO) has been used as a definitive noninvasive diagnostic tool in nearly all children. ECHO assesses cardiac ventricular size, wall thickness, systolic and diastolic function, and outflow obstruction. Thus, ECHO has been chosen as an ideal means to detect excessive wall thickening of cardiac muscle in HCM.[74]
In HCM, treatment strategies aimed to reduce disease symptoms and lower the risk of sudden death.[77] Due to the heterogeneity of the disease, treatment is usually modified according to individual patients needs.[77] β-blockers improve left ventricular filling and relaxation and thereby improve symptoms. In some pediatric patients, β–blockers drugs (e.g. propranolol) were shown to effectively reduce the risk of sudden death.[77] Further, calcium channel blockers (verapamil) and antiarrhythmic drugs maybe used as an adjunct therapy to β-blockers in symptomatic children. Nonetheless, further testing is needed to determine their definitive benefits.[77]
==[edit] In other animals==
Echocardiography of Hypertrophic-obstructive cardiomyopathy (HOCM) in a cat.Feline hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats; the disease process and genetics are believed to be similar to the disease in humans.[78] In Maine Coon and American Shorthair cat breeds, HCM has been confirmed as an autosomal dominant inherited trait.[79] The first genetic mutation (in cardiac myosin binding protein C) responsible for feline hypertrophic cardiomyopathy was discovered in 2005 in Maine Coon cats.[80] A test for this mutation is available.[81] 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.[82]
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 [83] (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.
Category:Medical & Preventive Care