Hypertrophic cardiomyopathy

From Academic Kids

Hypertrophic cardiomyopathy, or HCM, is a disease of the myocardium (the muscle of the heart) in which a portion of the myocardium is hypertrophied (thickened) without any obvious cause.1 It is the leading cause of sudden cardiac death in young athletes in the United States.2

A cardiomyopathy is any disease that primarily affects the muscle of the heart. In HCM, the normal alignment of muscle cells is disrupted, a phenomenon known as myocardial disarray. HCM also causes disruptions of the electrical functions of the heart. HCM is believed to be due to a mutation in one of many genes that results in a mutated myosin heavy chain, one of the components of the myocyte (the muscle cell of the heart). Depending on 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.

HCM is also known as idiopathic hypertrophic subaortic stenosis (IHSS) and hypertrophic obstructive cardiomyopathy (HOCM). A non-obstructive variant of HCM is apical hypertrophic cardiomyopathy 3, which is also known as nonobstructive hypertrophic cardiomyopathy and Japanese variant hypertrophic cardiomyopathy (since the first cases described were all in individuals of Japanese descent).

While most literature so far focuses on European, American, and Japanese populations, HCM appears in all racial groups. The incidence of HCM is about 0.2% to 0.5% of the general population.

Contents

Genetics

Hypertrophic cardiomyopathy is attributed to mutation in one of a number of genes that encode for one of the sarcomere proteins (usually effecting either the α or β myosin heavy chain on chromosome 14 q11.2-3). While the severity of the disease process is dependent on the particular gene mutation, about 80% of cases are inherited in an autosomal dominant pattern. Other gene mutations that are associated with HCM include mutations in α-tropomyosin (on chromosome 15), troponin T (on chromosome 1), and myosin-binding protein C (on chromosome 11). The prognosis is variable, based on the gene mutation.

The MYH7 gene (encoding the Β-myosin heavy chain) was the first specific gene identified in familial hypertrophic cardiomyopathy. About 50 percent of all familial cases involve mutation in the MYH7 gene. In individuals without a family history of HCM, the most common cause of the disease is also mutations of the gene that produces the β-myosin heavy chain. Many different mutations in this gene have been identified, and the prognosis is dependant on the particular mutation.

An insertion/deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) has been associated with some cases of HCM. The D/D (deletion/deletion) genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of adverse outcomes.8,9

Anatomic characteristics

Individuals with HCM have some degree of left ventricular hypertrophy. Usually this is an asymmetric hypertrophy, involving the inter-ventricular septum, and is known as asymmetric septal hypertrophy (ASH). This is in contrast to the concentric hypertrophy seen in aortic stenosis or hypertension. About 2/3 of individuals with HCM have asymmetric septal hypertrophy.

Many individuals with HCM demonstrate an obstruction to the outflow of blood from the left ventricle. This is known as dynamic outflow obstruction, because the degree of obstruction is variable and is dependant on the amount of blood in the ventricle immediately before ventricle systole (contraction).

Dynamic outflow obstruction

Systolic anterior motion of the mitral valve

Echocardiogram demonstrating systolic anterior motion of the anterior leaflet of the mitral valve

Dynamic outflow obstruction (when present in HCM) is usually due to systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. During ventricular systole, the increased turbulence in the left ventricular outflow tract (LVOT) pulls the anterior leaflet of the mitral valve into the LVOT, towards the aortic valve. This extra tissue in the LVOT causes obstruction to the ejection of blood from the left ventricle.

Because the mitral valve leaflet doesn't get pulled into the LVOT until after the aortic valve opens, the initial upstroke of the arterial pulse will be normal. When the mitral valve leaflet gets pulled 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. The 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.

Associated symptoms

The symptoms of HCM include shortness of breath, chest pain (sometimes known as angina), uncomfortable awareness of the heart beat (palpitation), light-headedness, dizziness, blackouts and sudden cardiac death. These symptoms of HCM can be due to the outflow tract gradient, the increased thickness of the myocardium (muscle of the heart), or rhythm disturbances associated with HCM, any permutation of these factors.

Risk factors for sudden death in individuals with HCM include a young age at first diagnosis (age < 30 years), an episode of aborted sudden death, a family history of HCM with sudden death of relatives, specific mutations in the genes encoding for troponin T and myosin, sustained supraventricular or ventricular tachycardia, recurrent syncope, ventricular septal wall thickness over 3cm, hypotensive response to exercise, and bradyarrhythmias (slow rhythms of the heart).4

Physical examination

Differentiating hypertrophic cardiomyopathy and valvular aortic stenosis
Aortic stenosis Hypertrophic cardiomyopathy
Echocardiography
Aortic valve calcificationCommonNo
Dilated ascending aortaCommonRare
Ventricular hypertrophyConcentric LVHAsymmetric, often involving the septum
Physical examination
Murmur of AICommonNo
Pulse pressure afer PVCIncreasedDecreased
Valsalva maneuverDecreased intensity of murmurIncreased intensity of murmur
Carotid pulsationNormal or parvus et tardusBrisk, jerky

The physical findings of HCM are associated with the dynamic outflow obstruction that is often present with this disease.

Upon auscultation, the cardiac murmur will sound similar to the murmur of aortic stenosis. However, this murmur will increase in intensity with any maneuver that decreases the volume of blood in the left ventricle (such as standing or the strain phase of a Valsalva maneuver).

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

Diagnostic testing

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

Cardiac catheterization

Pressure tracings demonstrating the Brockenbrough-Braunwald-Morrow sign
Missing image
Hypertrophic_Cardiomyopathy_-_Intraventricular_Pressure_Tracing.png
Pressure tracings demonstrating the Brockenbrough-Braunwald-Morrow sign

AO = Descending aorta; LV = Left ventricle; ECG = Electrocardiogram.

After the third QRS complex, the ventricle has more time to fill. Since there is more time to fill, the left ventricle will have more volume at the end of diastole (increased preload). Due to the Frank-Starling law of the heart, the contraction of the left ventricle (and pressure generated by the left ventricle) will be greater on the subsequent beat (beat #4 in this picture). Because of the dynamic nature of the outflow obstruction in HCM, the obstruction increases more that the left ventricular pressure increase. This causes a fall in the aortic pressure as the left ventricular pressure rises (seen as the yellow shaded area in the picture).

Upon cardiac catheterization, catheters can be placed in the left ventricle and the ascending aorta, to measure the pressure difference between these structures. In normal individuals, during ventricular systole, the pressure in the ascending aorta and the left ventricle will equalize, and the aortic valve is open. In individuals with aortic stenosis or with HCM with an outflow tract gradient, there will be a pressure gradient (difference) between the left ventricle and the aorta, with the left ventricular pressure higher than the aortic pressure. This gradient represents the degree of obstruction that has to be overcome in order to eject blood from the left ventricle.

The Brockenbrough-Braunwald-Morrow sign is observed in individuals with HCM with outflow tract gradient. This sign can be used to differentiate HCM from aortic stenosis. In individuals with aortic stenosis, after a premature ventricular contraction (PVC), the following ventricular contraction will be more forceful, and the pressure generated in the left ventricle will be higher. Because of the fixed obstruction that the stenotic aortic valve represents, the post-PVC ascending aortic pressure will increase as well. In individuals with HCM, however, the degree of obstruction will increase more than the force of contraction will increase in the post-PVC beat. The result of this is that the left ventricular pressure increases and the ascending aortic pressure decreases, with an increase in the LVOT gradient.

While the Brockenbrough-Braunwald-Morrow sign is most dramatically demonstrated using simultaneous intra-cardiac and intra-aortic catheters, it can be seen on routine physical examination as a decrease in the pulse pressure in the post-PVC beat in individuals with HCM.

Treatment

Treatment of HCM is directed towards decreasing the left ventricular outflow tract gradient and to abort arrhythmias in individuals at high risk of sudden cardiac death.

A septal myectomy is a surgical procedure that is performed in individuals with severe septal hypertrophy in order to decrease the left ventricular outflow tract obstruction. It involves removing a portion of the interventricular septum.

Alcohol septal ablation is a percutaneous technique that involves injection of alcohol into the first septal perferator 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.6

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.7

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

Related disorders

Feline hypertrophic cardiomyopathy is the most common heart disease in cats; the disease process and genetics are believed to be similar to the disease in humans.5

References

1. Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. 1996 Mar 1;93(5):841-2. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8598070)) (Full text (http://circ.ahajournals.org/cgi/content/full/93/5/841))

2. Maron BJ, Thompson PD, Puffer JC, McGrew CA, Strong WB, Douglas PS, Clark LT, Mitten MJ, Crawford MH, Atkins DL, Driscoll DJ, Epstein AE. Cardiovascular preparticipation screening of competitive athletes. A statement for health professionals from the Sudden Death Committee (clinical cardiology) and Congenital Cardiac Defects Committee (cardiovascular disease in the young), American Heart Association. Circulation. 1996 Aug 15;94(4):850-6. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8772711)) (Full text (http://circ.ahajournals.org/cgi/content/full/94/4/850))

3. Rivera-Diaz J, Moosvi AR. Apical hypertrophic cardiomyopathy. South Med J. 1996 Jul;89(7):711-3. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8685759)), (Full text (http://www.sma.org/smj/96jul12.htm))

4. Maron BJ, Cecchi F, McKenna WJ. Risk factors and stratification for sudden cardiac death in patients with hypertrophic cardiomyopathy. Br Heart J. 1994 Dec;72(6 Suppl):S13-8. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=7873317)) and the Task Force on Sudden Cardiac Death of the European Society of Cardiology (http://www.guideline.gov/summary/summary.aspx?doc_id=2977).

5. Kittleson MD, Meurs KM, Munro MJ, Kittleson JA, Liu SK, Pion PD, Towbin JA. Familial hypertrophic cardiomyopathy in maine coon cats: an animal model of human disease. Circulation. 1999 Jun 22;99(24):3172-80. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10377082))

6. Brilakis ES, Nishimura RA. Severe pulmonary hypertension in a patient with hypertrophic cardiomyopathy: response to alcohol septal ablation. Heart. 2003 Jul;89(7):790. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12807862))

7. Ommen SR, Nishimura RA, Squires RW, Schaff HV, Danielson GK, Tajik AJ. Comparison of dual-chamber pacing versus septal myectomy for the treatment of patients with hypertropic obstructive cardiomyopathy: a comparison of objective hemodynamic and exercise end points. J Am Coll Cardiol. 1999 Jul;34(1):191-6. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10400010))

8. Doolan G, Nguyen L, Chung J, Ingles J, Semsarian C. Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy. Int J Cardiol. 2004 Aug;96(2):157-63. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15314809))

9. Marian AJ, Yu QT, Workman R, Greve G, Roberts R. Angiotensin-converting enzyme polymorphism in hypertrophic cardiomyopathy and sudden cardiac death. Lancet. 1993 Oct 30;342(8879):1085-6. (Medline abstract (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8105312))

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