Hypertrophic Cardiomyopathy 

Updated: Jan 05, 2016
Author: Sandy N Shah, DO, MBA, FACC, FACP, FACOI; Chief Editor: Henry H Ooi, MD, MRCPI 

Overview

Practice Essentials

Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disease. It is defined by an increase in left ventricular wall thickness that is not solely explained by abnormal loading conditions. This disorder is caused by a mutation in cardiac sarcomere protein genes and is most frequently transmitted as an autosomal dominant trait. HCM has a variable presentation.

Signs and symptoms

Signs and symptoms of HCM can include the following:

  • Sudden cardiac death (the most devastating presenting manifestation)

  • Dyspnea (the most common presenting symptom)

  • Syncope and presyncope

  • Angina

  • Palpitations

  • Orthopnea and paroxysmal nocturnal dyspnea (early signs of congestive heart failure [CHF])

  • CHF (relatively uncommon but sometimes seen)

  • Dizziness

Physical findings may include the following:

  • Double apical impulse or triple apical impulse (less common)

  • Normal first heart sound; second heart sound usually is normally split but is paradoxically split in some patients with severe outflow gradients; S3 gallop is common in children but signifies decompensated CHF in adults; S4 is frequently heard

  • Jugular venous pulse revealing a prominent a wave

  • Double carotid arterial pulse

  • Apical precordial impulse that is displaced laterally and usually is abnormally forceful and enlarged

  • Systolic ejection crescendo-decrescendo murmur

  • Holosystolic murmur at the apex and axilla of mitral regurgitation

  • Diastolic decrescendo murmur of aortic regurgitation (10% of patients)

See Clinical Presentation for more detail.

Diagnosis

No specific laboratory blood tests are required in the workup. Genetic testing is not yet widely available but is becoming increasingly so.

Two-dimensional (2-D) echocardiography may be diagnostic for HCM. Findings may be summarized as follows:

  • Abnormal systolic anterior leaflet motion of the mitral valve

  • Left ventricular hypertrophy (LVH)

  • Left atrial enlargement

  • Small ventricular chamber size

  • Septal hypertrophy with septal-to-free wall ratio greater than 1.4:1

  • Mitral valve prolapse and mitral regurgitation

  • Decreased midaortic flow

  • Partial systolic closure of the aortic valve in midsystole

Other imaging modalities that may be useful include the following:

  • Chest radiography

  • Radionuclide imaging

  • Cardiac magnetic resonance imaging: Particularly useful when echocardiography is questionable, particularly with apical hypertrophy

Electrocardiographic findings may include the following:

  • ST-T wave abnormalities and LVH (common)

  • Axis deviation (right or left)

  • Conduction abnormalities (P-R prolongation, bundle-branch block)

  • Sinus bradycardia with ectopic atrial rhythm

  • Atrial enlargement

  • Abnormal and prominent Q wave in the anterior precordial and lateral limb leads, short P-R interval with QRS suggestive of preexcitation, atrial fibrillation (poor prognostic sign), and a P-wave abnormality (all uncommon)

The following diagnostic modalities may also be useful:

  • Cardiac catheterization (to determine the degree of outflow obstruction, cardiac hemodynamics, the anatomy and diastolic characteristics of the left ventricle, and the coronary anatomy)   

  • Electrophysiologic studies

See Workup for more detail.

Management

Pharmacologic therapy for HCM may include the following:

  • Beta blockers

  • Calcium channel blockers

  • Diltiazem, amiodarone, and disopyramide (rarely)

  • Antitussives to prevent coughing

The following caveats are warranted:

  • Avoid inotropic drugs if possible

  • Avoid nitrates and sympathomimetic amines, except in concomitant coronary artery disease

  • Avoid digitalis

  • Use diuretics with caution

Surgical and catheter-based therapeutic options include the following:

  • Left ventricular myomectomy

  • Mitral valve replacement

  • Permanent pacemaker implantation

  • Catheter septal ablation

  • Placement of an implantable cardioverter defibrillator

  • Heart transplantation

See Treatment and Medication for more detail.

Background

Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is typically inherited in an autosomal dominant fashion with variable penetrance and variable expressivity. The disease has complex symptomatology and potentially devastating consequences for patients and their families.[1] (See Etiology and Prognosis.)

The disorder has a variable presentation and carries a high incidence of sudden death. In fact, HCM is the leading cause of sudden cardiac death in preadolescent and adolescent children. The hallmark of the disorder is myocardial hypertrophy that is inappropriate, often asymmetrical, and occurs in the absence of an obvious inciting hypertrophy stimulus. This hypertrophy can occur in any region of the left ventricle but frequently involves the interventricular septum, which results in an obstruction of flow through the left ventricular (LV) outflow tract. (See Prognosis, History, Physical Examination, and Workup.)

Decades ago, HCM was written about and known as idiopathic hypertrophic subaortic stenosis (IHSS) or asymmetrical septal hypertrophy (ASH). These terms were replaced by hypertrophic cardiomyopathy, because the segmental hypertrophy can occur in any segment of the ventricle, not just the septum. Furthermore, this entity can present without subaortic obstruction to flow yet still carry the same ominous risk of arrhythmogenic sudden death and many of its clinical symptoms.

HCM can be separated into obstructive and nonobstructive types. Obstructive HCM is due to midsystolic obstruction of flow through the LV outflow tract as a result of a Bernoulli effect–induced systolic anterior mitral valve movement toward the septum.

The significance of this obstruction, however, is highly controversial. Some investigators and experts believe the obstruction has less to do with the overall hemodynamic and pathophysiologic manifestations of this entity than it does with the inappropriate segmental hypertrophy, which, with its increased myocardial oxygen consumption and substrate for fatal ventricular arrhythmias, has much more significance in the overall clinical picture of this entity and in the treatment and prognosis of HCM.

HCM is a familial disease.[2] There are defects in several of the genes encoding for the sarcomeric proteins, such as myosin heavy chain, actin, tropomyosin, and titin.[3, 4] Multiple mutations have been identified, with genotype-specific risks for mortality and degree of hypertrophy. Interestingly, the genetic basis of ventricular hypertrophy does not directly correlate with prognostic risk stratification. (See Etiology.)

Patients with some mutations, such as specific tropomyosin substitutions, have only a mild degree of ventricular hypertrophy, with little or no LV outflow tract obstruction, but they still carry a disproportionately high risk for sudden death.[5]

Many patients, particularly children, with HCM may not be symptomatic. Careful evaluation of a heart murmur may reveal the condition. (See Physical Examination and Workup.)

Complications

Complications of HCM may include the following:

  • Congestive heart failure

  • Ventricular and supraventricular arrhythmias

  • Infective mitral endocarditis

  • Atrial fibrillation with mural thrombus formation

  • Sudden death

Pathophysiology

Since the initial descriptions of hypertrophic cardiomyopathy (HCM), the feature that has attracted the greatest attention is the dynamic pressure gradient across the LV outflow tract. The pressure gradient appears to be related to further narrowing of an already small outflow tract (already narrowed by the marked asymmetrical septal hypertrophy and possibly by an abnormal location of the mitral valve) by the systolic anterior motion of the mitral valve against the hypertrophied septum.

Three explanations for the systolic anterior motion of the mitral valve have been offered, as follows: (1) the mitral valve is pulled against the septum by contraction of the papillary muscles, which occurs because of the valve's abnormal location and septal hypertrophy altering the orientation of the papillary muscles; (2) the mitral valve is pushed against the septum because of its abnormal position in the outflow tract; (3) the mitral valve is drawn toward the septum because of the lower pressure that occurs as blood is ejected at high velocity through a narrowed outflow tract (Venturi effect).

Most patients with HCM have abnormal diastolic function (whether or not a pressure gradient is present), which impairs ventricular filling and increases filling pressure, despite a normal or small ventricular cavity. These patients have abnormal calcium kinetics and subendocardial ischemia, which are related to the profound hypertrophy and myopathic process.

Etiology

Abnormal calcium kinetics

Data link abnormal myocardial calcium kinetics to the cause of the inappropriate myocardial hypertrophy and specific features of HCM, particularly in patients with diastolic functional abnormalities. Abnormal myocardial calcium kinetics and abnormal calcium fluxes from an increase in the number of calcium channels result in an increase in intracellular calcium concentration, which, in turn, may produce hypertrophy and cellular disarray.

Genetic causes

Familial HCM occurs as an autosomal dominant Mendelian-inherited disease in approximately 50% of cases. Some, if not all, of the sporadic forms of the disease may be caused by spontaneous mutations.

At least 6 different genes on at least 4 chromosomes are associated with HCM, with more than 50 different mutations discovered thus far. Familial HCM is a genetically heterogenous disease in that it can be caused by genetic defects at more than 1 locus.

In 1989, Seidman and collaborators first reported the genetic basis for HCM. They reported the existence of a disease gene located on the long arm of chromosome 14. Subsequently, they found this to be the gene encoding for beta cardiac myosin heavy chain.

Wide variation exists in the phenotypic expression of a given mutation of a given gene, with variability in clinical symptoms and the degree of hypertrophy expressed. Phenotypic variability is related to the differences in genotype, with specific mutations associated with particular symptoms, the degree of hypertrophy, and the prognosis.[6]

Other possible causes

Other possible causes of HCM include the following:

  • Abnormal sympathetic stimulation - Heightened responsiveness of the heart to the excessive production of catecholamines or the reduced neuronal uptake of norepinephrine might cause HCM

  • Abnormally thickened intramural coronary arteries - These do not dilate normally, which leads to myocardial ischemia; this progresses to myocardial fibrosis and abnormal compensatory hypertrophy

  • Subendocardial ischemia - This is related to abnormalities of the cardiac microcirculation that deplete the energy stores essential for the sequestration of calcium during diastole; subendocardial ischemia results in persistent interaction of the contractile elements during diastole and increased diastolic stiffness

  • Cardiac structural abnormalities - These include a catenoid configuration of the septum, which results in myocardial cell hypertrophy and disarray

Epidemiology

Hypertrophic cardiomyopathy (HCM) is reported in 0.5% of the outpatient population referred for echocardiography.[7] The overall prevalence of HCM is low and has been estimated to occur in 0.05-0.2% of the population.[8] Morphologic evidence of disease is found by echocardiography in approximately 25% of first-degree relatives of patients with HCM. Genetic testing still is in the early stages of research development but can be used to identify asymptomatic family members with the same mutation as the proband (index case).

Sex-related demographics

HCM is slightly more common in males than in females. However, the genetic inheritance pattern is autosomal dominant, without sex predilection. Modifying genetic, hormonal, and environmental factors may lead to a higher likelihood of identification in males, increased symptomatology, or higher degrees of LV outflow obstruction, with more prominent findings upon physical examination.

HCM usually presents at a younger age in females. Females tend to be more symptomatic and are more likely to be disabled by their symptoms than males.

Age-related demographics

In general, HCM has a bimodal peak of occurrence. The most common presentation is in the third decade of life, but it may present in persons of any age, from newborns to elderly individuals.

In children, inherited cases are found in an age range from newborn (ie, stillborn babies) to adult. The peak incidence is in these cases is in the second decade of life.

In adults, the peak incidence is in the third decade of life, with the vast majority of cases occurring in the age range between the third and sixth decades of life.

Prognosis

Reported annual mortality rates in patients with hypertrophic cardiomyopathy (HCM) have ranged from less than 1% to 3-6%, and studies suggest that they have significantly improved over the past 40 years.[9]

A 2006 study reported that published sudden death rates over the previous 10 years were lower than were previously published figures (median 1.0% (range 0.1–1.7) v 2.0% (0–3.5)). Nevertheless, HCM still carries a high risk for mortality and morbidity.[10]

One series of 46 patients with midventricular obstruction was found to have an increased risk of apical aneurysm formation, symptoms, and HCM-related death compared with those who did not have midventricular obstruction; the increased risk of symptoms and death was similar to that seen in patients with LV outflow obstruction.[11]

Most patients with HCM are asymptomatic. Unfortunately, the first clinical manifestation of the disease in such individuals may be sudden death, likely from ventricular tachycardia or fibrillation. Younger patients, particularly children, have a much higher mortality rate. Children have a much greater degree of ventricular hypertrophy and are much more symptomatic early on in the disease course, most likely because more malignant genotypes are present earlier in life.

The more benign mutations do not elicit a clinical or echocardiographic phenotype or symptoms in the pediatric population. Death often is sudden, unexpected, and typically is associated with sports or vigorous exertion. Early diagnosis is of prime importance in order to prescribe an appropriate level of safe activity.[6, 12, 13]

Screening of first-degree relatives is useful to identify additional affected family members prior to the onset of significant symptoms or sudden death.

Patients can have a myriad of arrhythmias, including atrial fibrillation, atrial flutter, ventricular ectopy, ventricular tachycardia, and ventricular fibrillation. These patients are among the highest-risk group for ventricular fibrillation and pose difficult therapeutic decisions for risk reduction.

Patients have a high likelihood of recurrent heart failure resulting from mitral regurgitation and profound diastolic dysfunction. HCM is a progressive condition that worsens over time, as does the gradient across the LV outflow tract if left untreated. Systolic function usually is well preserved until the late stages of the disease. Angina is rare in children but common in adults. Syncope and presyncope are common and may identify individuals at high risk for sudden death.

Patient Education

Family members should learn cardiopulmonary resuscitation. In addition, refer the patient and family for psychosocial counseling. Refer children of patients with hypertrophic cardiomyopathy (HCM), especially those in the pediatric age range, for urgent echocardiography and genetic testing if an echocardiogram does not yet reveal overt disease.

Impose activity restrictions that include total abstinence from highly competitive athletic activities and very strenuous physical exertion, such as lifting heavy objects, lifting weights, and shoveling snow.

For patient education information, see the Heart Health Center, as well as Palpitations.

 

Presentation

History

Symptoms of hypertrophic cardiomyopathy (HCM) can include dyspnea, syncope and presyncope, angina, palpitations, orthopnea, paroxysmal nocturnal dyspnea, congestive heart failure, dizziness, and sudden cardiac death.

Sudden cardiac death

This is the most devastating presenting manifestation of HCM. It has the highest incidence in preadolescent and adolescent children and is particularly related to extreme exertion. The risk of sudden death in children is as high as 6% per year.

In more than 80% of cases, the arrhythmia that causes sudden death is ventricular fibrillation. Many of these cases degenerate into ventricular fibrillation from rapid atrial arrhythmias, such as fibrillation, supraventricular tachycardia, or Wolff-Parkinson-White syndrome, while others result from ventricular tachycardia and low cardiac output hemodynamic collapse.

Dyspnea

This is the most common presenting symptom, occurring in as many as 90% of symptomatic patients. Dyspnea largely is a consequence of elevated LV diastolic filling pressures (and transmission of those elevated pressures back into the pulmonary circulation). The elevated LV filling pressures principally are caused by impaired diastolic compliance as a result of marked hypertrophy of the ventricle.

Syncope

Syncope is a very common symptom, resulting from inadequate cardiac output upon exertion or from cardiac arrhythmia. It occurs more commonly in children and young adults with small LV chamber size and evidence of ventricular tachycardia upon ambulatory monitoring.

Alternatively, syncope may be caused by arrhythmias, either tachycardias or bradycardias. Some patients with HCM have abnormalities in sinus node function, leading to sick sinus syndrome with alternating tachyarrhythmias and bradyarrhythmias or severe bradyarrhythmias.

Syncope and presyncope identify patients at high risk of sudden death and warrant an urgent workup and aggressive treatment.

Presyncope

Presyncope includes "graying-out" spells that occur in the erect posture and can be relieved by immediately lying down. They occur quite commonly and identify patients at high risk for sudden death. These symptoms are exacerbated by vagal stimulation. Presyncope also may occur with nonsustained atrial or ventricular tachyarrhythmias.

Angina

Typical symptoms of angina are quite common in patients with HCM and may occur in the absence of detectable coronary atherosclerosis. Impaired diastolic relaxation and markedly increased myocardial oxygen consumption are caused by ventricular hypertrophy that results in subendocardial ischemia, particularly during exertion.

Palpitations

Palpitations are common. These result from arrhythmias, such as premature atrial and ventricular beats, sinus pauses, atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular tachycardia.

Orthopnea and paroxysmal nocturnal dyspnea

These are early signs of congestive heart failure and, while relatively uncommon, are observed in patients with severe HCM. They result from impaired diastolic function and elevated LV filling pressure. Orthopnea and paroxysmal nocturnal dyspnea result from pulmonary venous congestion.

Congestive heart failure

This is relatively uncommon but is observed in patients with severe HCM. It may occur as a result of a combination of impaired diastolic function and subendocardial ischemia. Systolic function in these patients almost always is well preserved.

Dizziness

Dizziness is common in patients with HCM with elevated pressure gradients across the LV outflow tract. It is worsened by exertion and may be exacerbated by hypovolemia following high levels of exertion or increased insensible fluid loss (eg, during extreme heat).

Dizziness also may occur as a result of maneuvers, such as rapid standing or Valsalva during defecation, or certain medications, such as diuretics, nitroglycerin, and vasodilating antihypertensive agents, that decrease preload and afterload and increase the pressure gradient across the LV outflow tract.

Dizziness also may be secondary to arrhythmia-related hypotension and decreased cerebral perfusion. Nonsustained arrhythmias often cause symptoms of dizziness, lightheadedness, and presyncope, whereas sustained arrhythmias are more likely to lead to syncope, collapse, and/or sudden cardiac death.

Physical Examination

Double apical impulse results from a forceful left atrial contraction against a highly noncompliant left ventricle. This occurs quite commonly in adults. Triple apical impulse results from a late systolic bulge that occurs when the heart is almost empty and is performing near-isometric contraction. This is a highly characteristic finding of hypertrophic cardiomyopathy (HCM); however, it occurs less frequently than does the double apical impulse.

First heart sound is normal. Second heart sound usually is normally split, but in some patients with severe outflow gradients, it is paradoxically split.

An S3 gallop is common in children, but it does not have the same ominous significance as in patients with valvular aortic stenosis. When it occurs in adults, it signifies decompensated congestive heart failure. A fourth heart sound, an S4, frequently is heard and results from atrial systole against a highly noncompliant left ventricle.

Jugular venous pulse reveals a prominent a wave caused by diminished right ventricular compliance secondary to massive hypertrophy of the ventricular septum.

Double carotid arterial pulse is common. The carotid pulse rises quickly because of the increased velocity of blood through the LV outflow tract and into the aorta. The carotid pulse then declines in midsystole as the gradient develops. This is followed by a secondary rise in carotid pulsation during late systole.

Apical precordial impulse frequently is displaced laterally and usually is abnormally forceful and enlarged.

Systolic ejection murmur typically is a systolic ejection crescendo-decrescendo murmur, which is best heard between the apex and left sternal border and radiates to the suprasternal notch but not to the carotid arteries or neck. The murmur and the gradient across the LV outflow tract diminish with any increase in preload (eg, Mueller maneuver, squatting) or increase in afterload (eg, handgrip). The murmur and the gradient increase with any decrease in preload (eg, Valsalva maneuver, nitrate administration, diuretic administration, standing) or with any decrease in afterload (eg, vasodilator administration).

Holosystolic murmur at the apex and axilla of mitral regurgitation is heard in patients with systolic anterior motion of the mitral valve and significant LV outflow gradients. Diastolic decrescendo murmur of aortic regurgitation is heard in 10% of patients, although mild aortic regurgitation can be detected by Doppler echocardiography in 33% of patients.

 

DDx

 

Workup

Approach Considerations

Two-dimensional (2-D) echocardiography is diagnostic for hypertrophic cardiomyopathy (HCM). In general, a summary of echocardiography findings includes abnormal systolic anterior leaflet motion of the mitral valve, LV hypertrophy, left atrial enlargement, small ventricular chamber size, septal hypertrophy with septal-to-free wall ratio greater than 1.4:1, mitral valve prolapse and mitral regurgitation, decreased midaortic flow, and partial systolic closure of the aortic valve in midsystole.

No specific laboratory blood tests are required in the workup of HCM; however, routine laboratory tests may assist in the evaluation of the etiology and/or exacerbating factors contributing to the LV dysfunction. Genetic testing is not widely available at present, but it is becoming increasingly available in this disease setting. In research situations or in larger pedigrees, genotyping is informative for the identification of additional family members once the proband's genotype has been determined.

Laboratory Studies

First-line laboratory tests are similar in adults and children.[14]  Routine laboratory studies may aid in the evaluation of the etiology and/or exacerbating factors underlying the left ventricular (LV) dysfunction.

  • Hemoglobin level: Anemia exacerbates chest pain and dyspnea
  • Fasting glucose levels
  • Renal function tests: Impaired renal function may be seen with severe LV dysfunction
  • Liver function tests (LFT)
  • Brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and troponin T levels: Elevated BNP, NT-proBNP, and troponin T levels are associated with a higher risk of cardiovascular events, heart failure, and death
  • Thyroid function tests: In patients on amiodarone, thyroid studies should be obtained at the time of diagnosis and monitored every 6 months 

Additional laboratory tests can be performed after a specialist evaluation, as needed.

Two-Dimensional Echocardiography and Doppler Studies

As stated, 2-D echocardiography is diagnostic for hypertrophic cardiomyopathy (HCM). Color Doppler flow studies typically reveal mitral regurgitation.[15]

Spectral continuous-wave Doppler studies in patients with obstructive HCM reveal an elevated flow velocity across the LV outflow tract. Severe obstructive HCM typically has a flow velocity greater than 4 m/s, and a gradient across the LV outflow tract of greater than 50 mm Hg is considered severe.

Echocardiography also typically reveals diastolic dysfunction with reduced LV compliance and a mitral valve ratio of E wave to A wave of less than 1 (usually < 0.8). Systolic function is typically well preserved and normal, and, in fact, the LV ejection fraction is usually normal or high at the time of diagnosis. The LV diameter is at the lower limit of normal or smaller than normal.

A study by Peteiro et al suggests that assessing exercise capacity and LV systolic function during exercise echocardiography may aid in determining the risk stratification among patients with hypertrophic cardiomyopathy.[16]

Tissue Doppler imaging is quite useful as a screening tool in patients with morphologically normal ventricles and in differentiating HCM from other causes of LV hypertrophy (ie, athletic heart hypertrophy).

The hallmarks of the obstructive type of HCM consist of systolic anterior motion of the anterior mitral valve leaflet, septal wall thickness of >15 mm, and asymmetrical septal hypertrophy with a ratio of septal wall thickness to posterior wall thickness of greater than 1.4:1.

The septum not only is relatively thicker than the posterior wall, it is also typically at least 4-6 mm thicker than normal for each age group. Massive hypertrophy with septal wall thickness of greater than 25 mm has been noted in rare cases, particularly in infants with glycogen storage defects, as are observed in patients with Pompe disease.

An unusual echocardiographic pattern consisting of a ground-glass appearance has been noted in portions of the hypertrophied myocardium in some patients. This pattern may be related to the abnormal cellular architecture and myocardial fibrosis that have been observed in pathologic studies.

A narrowing of the LV outflow tract occurs in many patients with HCM. This contributes to the creation of a pressure gradient in a small number of patients.

The hallmark of HCM associated with a pressure gradient is the abnormal systolic motion of the anterior leaflet of the mitral valve (ie, systolic anterior motion) and, in rare cases, the systolic motion of the posterior leaflet.

Several other echocardiographic findings may be present in patients with HCM. For example, a small LV cavity may be present secondary to marked hypertrophy of the myocardium and encroachment into the LV cavity. Moreover, reduced septal motion and thickening during systole may occur, particularly of the upper septum, resulting from disarray of the myofibrillar architecture and abnormal contractile function.

The motion of the posterior wall may be normal or increased, and the rate of closure of the mitral valve in middiastole may be reduced secondary to a decrease in LV compliance or abnormal transmitral flow during diastole. In addition, mitral valve prolapse, a rare echocardiographic occurrence in HCM, may be present.

Partial systolic closure or, more commonly, coarse systolic fluttering of the aortic valve related to turbulent blood flow in the outflow tract may occur. Abnormalities in diastolic function may be demonstrated by echocardiography and Doppler recordings in approximately 80% of patients with HCM, independent of the presence or absence of a systolic pressure gradient.

The presence of mitral regurgitation virtually always is confirmed by Doppler echocardiography in patients with HCM who have a systolic gradient.

Chest Radiography and Radionuclide Imaging

Chest radiography

Chest radiograph (CXR) findings are variable. The cardiac silhouette may range from normal to markedly increased in size. Left atrial enlargement frequently is observed, especially when significant mitral regurgitation is present. This is manifested by a "double-density" appearance on CXR.

Radionuclide imaging

Radionuclide imaging with thallium or technetium may show reversible defects, mostly in the absence of coronary artery disease. Thallium or technetium scintigraphy may reveal defects in myocardial perfusion, even in the setting of angiographically normal coronary arteries.

These reversible defects evident on radionuclide scanning are more common in children and adolescents with a history of sudden death or syncope, which suggests that myocardial ischemia is a significant factor in the mechanism of the demise of younger patients with HCM.

Cardiac MRI

Cardiac MRI imaging is very useful in the diagnosis and assessment of hypertrophic cardiomyopathy (HCM), with ideal image quality covering both ventricles completely for localization of hypertrophy. Cardiac MRI is particularly useful when echocardiography is questionable, particularly with apical hypertrophy.

Cines, oriented in the plane of the LV outflow tract, typically show obstruction, and velocity mapping is useful in the assessment of peak velocities. Systolic anterior motion of the mitral valve is clearly seen on cardiac MRI.

Improvement in obstruction after septal ablation or myomectomy can be demonstrated, as can the location and size of the associated infarction, which are useful for planning repeat procedures.

Cardiac MRI tagging identifies abnormal patterns of strain, shear, and torsion in cases of HCM, demonstrating significant dysfunction in hypertrophic areas of the ventricle. Cardiovascular MR spectroscopy reveals bioenergetic defects in HCM patients with varying genetic mutations, a fact that supports the hypothesis that the underlying substrate for HCM may be inefficient energy utilization.

The accuracy of the phenotypic determination of HCM by cardiac MRI is helpful for family screening, and genetic linkage studies for causative mutations are improved in power.

The use of gadolinium contrast in cardiac MRI is very useful in differentiating HCM from other causes of cardiac hypertrophy and other types of cardiomyopathy, such as amyloidosis, athletic heart, and Fabry disease (alpha-galactoside deficiency).

Late gadolinium enhancement occurring in HCM represents myocardial fibrosis. The greater the degree of late gadolinium enhancement, the more likely that the particular HCM patient has 2 or more risk factors for sudden death and the more likely the patient has or will develop progression of ventricular dilation toward heart failure, thereby indicating a poorer prognosis.

Most patients with HCM have no gadolinium enhancement; a common benign pattern is 2 stripes running along the junction of the right ventricle insertion into the left ventricle.

More extensive gadolinium enhancement can be dense and plaquelike or diffuse. The greater the gadolinium enhancement, the higher the risk of heart failure or sudden death, presumably from reentrant tachycardias and systolic failure from myocyte replacement.

Fabry disease (alpha-galactoside deficiency), which occurs in approximately 4% of HCM patients, often shows unusual lateral wall gadolinium enhancement on cardiac MRI.

Electrocardiography

Common electrocardiographic findings include ST-T wave abnormalities and LV hypertrophy. Other findings observed on ECG include axis deviation (right or left), conduction abnormalities (P-R prolongation, bundle-branch block), sinus bradycardia with ectopic atrial rhythm, and atrial enlargement. One mutation has been identified that is associated with hypertrophic cardiomyopathy (HCM) and Wolff-Parkinson-White syndrome.

Uncommon findings include an abnormal and prominent Q wave in the anterior precordial and lateral limb leads, short P-R interval with QRS suggestive of preexcitation, atrial fibrillation (poor prognostic sign), and a P-wave abnormality, including left atrial enlargement.

Findings on Holter monitoring and event electrocardiography commonly include atrial and ventricular ectopy, sinus pauses, wandering atrial pacemaker, atrial tachycardia, atrial fibrillation and/or flutter, and nonsustained ventricular tachycardia.

Comprehensive cardiovascular MRI examination can find the presence of scar and may be a good independent predictor of all-cause and cardiac mortality in low or asymptomatic patients with HCM.[17]

Cardiac Catheterization

Although not required for the diagnosis of hypertrophic cardiomyopathy, a diagnostic cardiac catheterization is useful to determine the degree of outflow obstruction, cardiac hemodynamics, the diastolic characteristics of the left ventricle and LV anatomy, and, of particular importance, the coronary anatomy. Cardiac catheterization is also reserved for situations when invasive modalities of therapy, such as a pacemaker or surgery, are being considered.

Therapeutic cardiac catheterization interventions, utilized in well selected cases of hypertrophic cardiomyopathy, include transcatheter septal alcohol ablation to relieve the LV outflow obstruction by intentional infarction of a portion of the interventricular septum.

Cardiac catheterization frequently reveals diminished diastolic LV compliance and, in cases of obstructive hypertrophic cardiomyopathy, a systolic intracavitary pressure gradient within the body of the left ventricle, related to subaortic systolic anterior motion of the mitral valve abutting the markedly hypertrophied septum. The subaortic pressure gradient may be quite labile and may vary between 0 and 175 mm Hg in the same patient under different conditions.

The arterial pressure tracing found on cardiac catheterization may demonstrate a "spike and dome" configuration similar to the carotid pulse recording. As a consequence of diminished left ventricular compliance, the mean left atrial pressure and, particularly, the a wave, in the left atrial pressure pulse and left ventricular end-diastolic pressures are usually elevated.

Artifactual outflow gradients may occur if the left ventricular catheter becomes entrapped in the trabeculae of a markedly hypertrophied left ventricle.

Cardiac output may be depressed in patients with long-standing severe gradients, but in the majority of patients, it is normal. Occasionally, cardiac output is elevated in patients with markedly hyperdynamic LV systolic function.

Hemodynamic abnormality in hypertrophic cardiomyopathy (HCM) is not limited to the left side of the heart. Approximately one fourth of patients demonstrate pulmonary hypertension. It is usually mild, but in some cases, it can be moderate to severe, due (at least in part) to elevated mean left atrial pressures resulting from diminished LV compliance. A pressure gradient in the right ventricular outflow tract occurs in approximately 15% of patients who have obstruction to LV outflow and appears to result from markedly hypertrophied right ventricular tissue. Right atrial and right ventricular end-diastolic pressures may be slightly elevated.

Outflow gradient variability

A feature characteristic of HCM is the variability and lability of the LV outflow gradient. A patient may demonstrate a large gradient on one occasion and have none at another time. In some patients without a resting gradient, it may be temporarily provoked.

Three basic mechanisms involved in the production of dynamic gradients include increased contractility, decreased preload, and decreased afterload. In many patients with HCM, the gradient is midventricular and may be intensified by increased contractility, which exerts a direct muscular sphincter action.

The stimuli that provoke or intensify LV outflow tract gradients in HCM generally improve myocardial performance in normal subjects and in patients with most other forms of heart disease. Conversely, reductions in contractility or increases in preload or afterload, which increased LV dimensions, reduce or abolish the LV outflow gradient.

One of the most potent stimuli for enhancing the LV outflow gradient is postextrasystolic potentiation, which may occur after a spontaneous premature contraction or be induced by mechanical stimulation with a catheter. The resultant increase in contractility in the beat after the extrasystole is so marked that it produces an increase in the outflow gradient. A characteristic change often occurs in the directly recorded arterial pressure tracing, which, in addition to displacing a more marked spike and dome configuration, exhibits a pulse pressure that fails to increase as expected or actually decreases (the so-called Brockenbrough-Braunwald phenomenon).

This is one of the more reliable signs of dynamic obstruction of the LV outflow tract. In some patients, the postextrasystolic murmur is attenuated despite an increase in the outflow gradient, apparently because, in this setting, the murmur mirrors to a greater degree changes in the severity of mitral regurgitation than changes in the outflow tract gradient.

Left ventriculography

Left ventriculography typically shows a hypertrophied ventricle and the presence of an outflow gradient. The anterior leaflet of the mitral valve moves anteriorly during systole and encroaches on the outflow tract. Associated with this motion is mitral regurgitation, which is a constant finding in patients with gradients. The LV cavity is often small, and systolic ejection is typically vigorous, resulting in virtual obliteration of the ventricular cavity at end systole. In patients with apical involvement, the extensive hypertrophy may convey a spade-like configuration to the left ventricular angiogram.

Other findings

In patients older than age 45 years, obstructive coronary artery disease may be present, although the symptoms of ischemic pain are indistinguishable from those of patients with normal coronary angiograms and HCM. The left anterior descending and septal perforator coronary arteries may demonstrate phasic narrowing and associated abnormalities of flow during systole

Electrophysiologic Studies

A diagnostic electrophysiology study using programmed electrical stimulation may identify conduction abnormalities, sinus node dysfunction (SND), and the potential for inducible arrhythmias.

The prognostic correlation of inducible arrhythmias with spontaneous clinical arrhythmias and/or sudden death is not entirely clear. Several studies have shown a relationship between electrophysiologic results and risk stratification for sudden cardiac death, but other studies have not been able to demonstrate a direct relationship.

Histologic Findings

Myocardial hypertrophy and gross disorganization of the muscle bundles result in a characteristic whorled pattern; cell-to-cell disarray and disorganization of the myofibrillar architecture within a given cell occur in almost all patients with hypertrophic cardiomyopathy (HCM).

Fibrosis is prominent and may be extensive enough to produce grossly visible scars. Abnormal intramural coronary arteries, with a reduction in the size of the lumen and thickening of the vessel wall, are common in patients with HCM, occurring in more than 80% of cases. This abnormality most frequently occurs in the ventricular septum and accompanies extensive fibrosis in the affected walls of the heart.

 

Treatment

Approach Considerations

Evaluation usually can be conducted on an outpatient basis. Inpatient studies and surgical treatment also may be necessary. Medical and surgical therapy are used to reduce ventricular contractility or increase ventricular volume, increase ventricular compliance and outflow tract dimensions, and, in the case of obstructive hypertrophic cardiomyopathy (HCM), reduce the pressure gradient across the LV outflow tract. Paramount to any therapy is reduction in the risk of sudden death by identification of these patients early on and effective medical and/or surgical implantation of an automatic defibrillator.[18]

Medications include beta blockers, calcium channel blockers, and, rarely, diltiazem, amiodarone, and disopyramide.[19] Antitussives may be administered as needed to avoid coughing.

Research shows that stepwise therapy can reduce high blood pressure in patients with HCM. In a study of 115 HCM patients, including 94 with obstructive HCM, stepwise antihypertensive therapy effectively controlled both obstructive HCM symptoms and hypertension. Average systolic pressure in the obstructive HCM group was reduced from 137 to 131 mm Hg, and uncontrolled hypertension was reduced from 56% at the first visit to 37% at the last.[20, 21]

Avoid inotropic drugs if possible; also avoid nitrates and sympathomimetic amines, except in those patients with concomitant coronary artery disease. Avoid digitalis, because glycosides are contraindicated except in patients with uncontrolled atrial fibrillation. Cautious use of diuretics should be exercised because of their potential adverse effect on the LV outflow gradient and ventricular volume.

American College of Cardiology Foundation/American Heart Association, Heart Rhythm Society, and European Society of Cardiology guidelines

The 2011 ACCF/AHA guidelines[22, 23] and the 2014 ESC guidelines[24] for the diagnosis and treatment of HCM are available here and here, respectively; and the 2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities[25] is available here.

Transfer

Transfer may be required for further diagnostic evaluation and electrophysiologic device or surgical intervention.

Deterrence/prevention

Patients must abstain from highly strenuous competitive athletic activity and highly strenuous physical exertion, such as shoveling snow or lifting very heavy objects, due to the high risk of arrhythmogenic sudden cardiac death. No acceptable medical recommendation deviates from total abstinence from these activities.

Consultations

Consultations may be indicated with the following specialists:

  • Cardiologist

  • Cardiothoracic surgeon

  • Cardiac electrophysiologist

  • Geneticist

Diet

No special diet is required. However, the patient should avoid excessive weight gain.

Invasive Therapies

2011 ACCF/AHA recommendations

The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding invasive therapies in patients with hypertrophic cardiomyopathy (HCM) are summarized below.[22, 23]

Class I recommendations

Only experienced operators should perform septal reduction therapy, in the setting of a dedicated HCM. Moreover, septal reduction therapy should be reserved for treatment-eligible patients with severe drug-refractory symptoms and left ventricular outlet tract (LVOT) obstruction. (Level of evidence: C)

Class IIa recommendations

It is reasonable to consult with centers experienced in performing surgical septal myectomy and alcohol septal ablation for treatment-eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction. At these centers, surgical septal myomectomy may be of benefit in symptomatic pediatric patients in whom traditional medical therapy has been ineffective. (Level of evidence: C)

Surgical septal myectomy performed in experienced centers is the first-line option for most treatment-eligible patients with HCM and severe drug-refractory symptoms and LVOT obstruction. Moreover, at these centers, adult patients with HCM and severe drug-refractory symptoms and LVOT obstruction who are not surgical candidates but who are eligible for alcohol septal ablation may benefit from this procedure (usually New York Heart Association [NYHA] class III or IV). (Level of evidence: B)

Class IIb recommendations

In experienced centers, following a detailed discussion with eligible adult patients with HCM and severe drug-refractory symptoms and LVOT obstruction, alcohol septal ablation may be a treatment option to surgical myectomy when the patient indicates a preference for septal ablation. (Level of evidence: B)

In general, alcohol septal ablation is discouraged in patients with HCM and marked (ie, >30 mm) septal hypertrophy owing to uncertainty regarding its efficacy in these patients. (Level of evidence: C)

Precautions (class III recommendations)

Note the following to prevent harm to patients with HCM (C level of evidence for all)[22, 23] :

  • Septal reduction therapy should only be performed as part of a dedicated HCM program.
  • Avoid septal reduction therapy in asymptomatic adults with HCM who have normal exercise tolerance or whose symptoms are controlled/minimized on medical therapy.
  • When septal reduction therapy is a feasible treatment option to relieve LVOT obstruction in eligible patients, do not perform mitral valve replacement as an alternative therapy.
  • Avoid performing alcohol septal ablation in (1) patients with HCM and comorbid conditions that also require surgical repair, in whom myectomy can be performed concomitantly; (2) pediatric patients with HCM (age <21 years); and (3) adults younger than 40 years in whom myectomy is a feasible alternative therapy.

Left Ventricular Myomectomy and Mitral Valve Replacement

Left ventricular myomectomy

Left ventricular (LV) myomectomy is used for patients with severe symptoms refractory to therapy and an outflow gradient of more than 50 mm Hg, either with provocation or with rest. The procedure typically is successful in abolishing the outflow gradient; most patients have symptomatic improvement for at least 5 years.

The reduction in LV outflow gradient may not correlate with a risk reduction for sudden death or overall mortality. Furthermore, the outflow gradient may increase gradually over time and return to the same level as before, requiring a repeat procedure or additional medical therapy.

Patients who have obstructive hypertrophic cardiomyopathy with low resting gradients and latent obstruction may have limiting symptoms similar to patients with more severe resting gradients. In a series of 749 patients undergoing septal myectomy, 249 had minimal gradients at rest but severe outflow tract obstruction with provocation testing. Symptom relief and survival in these patients was similar to that of patients with severe resting outflow obstruction undergoing myectomy. The authors suggest that septal myectomy may be recommended to patients who have severe outflow obstruction only on provocative testing because survival and symptom relief are excellent, suggesting that dynamic obstruction is the major hemodynamic problem and not diastolic dysfunction.[26]

In a retrospective study (1998-2010) that evaluated data from the Nationwide Inpatient Sample regarding the results of ventricular septal myectomy in patients iwth HCM with refractory LVOT obstruction, Panaich et al found an overall mortality of 5.9%; there was an association between age and severity of comorbidities with higher rates of complications and mortality.[27]

In a prospective observational study (1991-2012) that evaluated the long-term outcomes (8.3 ± 6.1 y) of myectomy combined with anterior mitral leaflet extension in severely symptomatic patients with HCM, Vriesendorp et al reported no operative mortality, with symptomatic relief similar to the general population.[28] Cumulative survival rates at 1 year were 98%; 5 years, 92%; 10 years, 86%; and 15 years, 83%.[28]

In a more recent systematic review and meta-analysis of 10 studies comprising 1824 patients for evaluating the efficacy and short- and long-term mortality of surgical myectomy (n = 1019) compared with alcohol septal ablation (n = 805}, Singh et al found no significant difference in symptomatic relief between the two procedures, and outocomes were similar for sudden cardiac death and short- and long-term mortality.[29]

Mitral valve replacement

Mitral valve replacement is reserved for patients with severe mitral regurgitation due to systolic anterior movement of the mitral valve, particularly when mitral regurgitation (large regurgitant fraction) is associated with the development of congestive heart failure or severe pulmonary hypertension.

Pacemaker Implantation

Pacemaker implantation has been a proposed treatment for patients with hypertrophic cardiomyopathy (HCM). Studies have shown that pacing the right ventricular RV apex to maintain atrioventricular synchrony results in a decrease of the left ventricular outflow tract (LVOT) gradient, with symptomatic and quality-of-life improvements.[22, 23] A Cochrane review suggested that the benefits of pacing are based on physiologic measures and lacks clinically relevant end-points.[30]

2011 ACCF/AHA recommendations

The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding pacing in patients with HCM are summarized below.[22, 23]

Class IIa recommendation

For patients with HCM who previously underwent dual-chamber device implantation for non–HCM-related causes, the ACCF/AHA believe a trial of dual-chamber atrial-ventricular pacing (from the right ventricular apex) for symptomatic relief from LVOT obstruction can be considered. (Level of evidence: B)

Class IIb recommendation

Permanent pacing is an option in symptomatic patients with medically refractory obstructive HCM who are not good candidates for septal reduction therapy. (Level of evidence: B)

Select patients in whom permanent pacemaker implantation is of no benefit (class III recommendations)

The 2011 ACCF/AHA guidelines indicate pacemaker implantation is not beneficial in the following scenarios for patients with HCM[22, 23] :

  • For reduction of the gradient in those who are asymptomatic or whose symptoms are medically-controlled (Level of evidence: C)
  • For first-line treatment of symptomatic relief in candidates eligible for septal reduction who have medically refractory disease and LVOT obstruction (Level of evidence: B)

Catheter Septal Ablation

Transvenous catheter ablation of the septal region has been performed using selective arterial ethanol infusion to destroy myocardial tissue.[31] The procedure involves infusing 96% ethanol down the first septal branch of the left anterior descending artery and inducing a therapeutic infarction of the proximal interventricular septal myocardium.

This leads to a remodeling of the septum, which decreases the marked septal thickening characteristic of hypertrophic cardiomyopathy (HCM) and results in a decrease of the gradient across the left ventricular outflow tract (LVOT). In this manner, the procedure is analogous to a surgical myomectomy, in attempting to decrease the amount of septal ventricular myocardium and thereby reducing the LVOT gradient.

The procedure has been used in clinical practice since the early 1990s and the reported results have been excellent, with significant reduction in symptoms, particularly in the incidence of heart failure.[32, 33] In many centers, it is the surgical procedure of choice for HCM.

Alcohol septal ablation

Alcohol septal ablation offers some advantages over surgical myectomy in that (1) it does not require surgical incision and/or general anesthesia, (2) the recovery time is shorter, and (3) its results lead to less discomfort and greater patient satisfaction than are reported with surgical myectomy.[22, 23] In addition, older patients who often have multiple comorbidities may better tolerate alcohol septal ablation than septal myectomy, which has high postoperative risks and complications in this patient population. Note that alcohol septal ablation is not indicated for the pediatric population.[22, 23]

The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding alcohol septal ablation in patients with HCM are summarized below.[22, 23]

Class I recommendations

As discussed earlier, it is reasonable to consult with centers experienced in performing alcohol septal ablation and surgical septal myectomy for treatment-eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction.

Use transthoracic (TTE) or transesophageal (TTE) echocardiography for intraoperative guidance of alcohol septal ablation (level of evidence: B) and TTE for assessing the outcomes of alcohol septal ablation (or surgical myectomy) in patients with obstruct HCM (level of evidence: C).

Class IIa recommendations

For clinical decision making and evaluation for the feasibility of alcohol septal ablation, use TEE when TTE findings are unclear.

Class IIb recommendations

In experienced centers, following a detailed discussion with eligible adult patients with HCM and severe drug-refractory symptoms and LVOT obstruction, alcohol septal ablation may be a treatment option to surgical myectomy when the patient indicates a preference for septal ablation. (Level of evidence: B)

In general, alcohol septal ablation is discouraged in patients with HCM and marked (ie, >30 mm) septal hypertrophy owing to uncertainty regarding its efficacy in these patients. (Level of evidence: C)

Class III recommendations

To prevent harm, avoid performing alcohol septal ablation in (1) patients with HCM and comorbid conditions that also require surgical repair, in whom myectomy can be performed concomitantly; (2) pediatric patients with HCM (age <21 years); and (3) adults younger than 40 years in whom myectomy is a feasible alternative therapy. (Level of evidence: C)

Complications of alcohol septal ablation and comparison to surgical myectomy

The European Society of Cardiology (ESC) indicates that the main nonfatal complication of alcohol septal ablation is atrioventricular block (7-20%); in addition, it is associated with 4-5–fold increased risk for permanent pacemaker, as well as right rather than left bundle branch block, compared to septal myectomy.[14] Moreover, although clinical and hemodynamic effects are seen immediately after setpal myectomy, they may be delayed for up to 3 months following alcohol septal ablation.

There appears to be little benefit to alcohol septal ablation in patients whose septal thickness is 30 mm or more (ie, severe HCM), as compared to septal myectomy.[14] The septal myectomy treatment approach visually assesses the anatomy of the LVOT and the mitral apparatus, whereas the alcohol septal ablation approach indirectly ablates the septal perforator artery distribution.

Overall, the procedural mortality for both procedures are similar.[14]

Implantable Cardioverter Defibrillator

Sudden cardiac death occurs in approximately 1% of patients with hypertrophic cardiomyopathy (HCM) each year, and pharmacotherapy has not shown protection against sudden cardiac death.[22, 23] However, high-risk individuals in whom prophylactic therapy may be indicated may potentially benefit from placement of an implantable cardioverter defibrillator (ICD), which can effectively terminate life-threatening ventricular tachyarrhythmias in the setting of HCM.[22, 23]

2011 ACCF/AHA recommendations

The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding ICD placement in patients with HCM are summarized below.[22, 23]

Class I recommendations

ICD placement decision making in patients with HCM should involve a comprehensive discussion between clinicians and patients. (Level of evidence: C)

This procedure is recommended for patients with HCM who have documentation of having suffered cardiac arrest, ventricular fibrillation, or hemodynamically significant VT. (Level of evidence: B)

Class IIa recommendations

ICD placement is a reasonable intervention for patients with HCM who also have (1) one or more first-degree relatives who suffered sudden cardiac death likely related to HCM, (2) an LV wall thickness of 30 mm or more, and (3) one or more recent unexplained syncopal events, as well as for (4) high-risk pediatric patients with HCM and a history of unexplained syncope or massive LV hypertrophy, or a family history of sudden cardiac death, with consideration of long-term ICD complication rates. (Level of evidence: C)

ICD placement is an option for select patients with other risk factors for other sudden cardiac death in addition to having (1) nonsustained VT (eg, age <30 y) or (2) HCM plus exercise-induced blood pressure anomalies. (Level of evidence: C)

For ICD-eligible patients with HCM, it is reasonable to place a single-chamber device in younger patients who do not require atrial or ventricular pacing, or a dual-chamber device (1) in patients with sinus bradycardia and/or paroxysmal atrial fibrillation or (2) predominantly in older patients with high resting outflow gradients (>50 mm Hg) and significant heart failure symptoms in whom right ventricular pacing has the potential beneficial effects. (Level of evidence: C)

Class IIb recommendations

ICD effectiveness remains unclear in patients with HCM who do not have other risk factors for sudden cardiac death but do have either (1) isolated bursts of nonsustained VT or (2) exercise-induced blood pressure anomalies, especially in the setting of significant LVOT. (Level of evidence: C)

Precautions (class III recommendations)

To prevent harm to patients with HCM, do not use ICD placement as either (1) a routine strategy in the absence of high-risk factors or (2) a strategy to allow participation in competitive athletic events. Do not place an ICD in those with a known HCM genotype but who are asymptomatic. (Level of evidence: C)

Complications associated with ICD in HCM

There is a 4% reported rate of ICD-associated complications (procedural and over the long term) per year.[22, 23, 34]  Early complications include the possibility of pneumothorax, pericardial effusion, pocket hematoma, acute pocket infection, and/or lead dislodgment. Complications that may arise late include upper extremity deep venous thrombosis, lead dislodgment, infection, a high defibrillation threshold that may require revision of the the lead, and receipt of inappropriate shocks.[22, 23, 34]

Pediatric patients appear to suffer a higher rate of inappropriate shocks and lead fractures than adults adults do, predominantly owing to the strain placed on the leads as the children grow and are active.[22, 23, 34]

Although the procedure to place ICDs is generally safe, defective generators have been known to cause death, high-voltage leads with small diameters have a tendency to fracture, and patients with severe hypertrophy or who are receiving amiodarone may need high-energy output generators or epicardial lead systems.[22, 23, 34]

Indications for Heart Transplantation

Heart transplantation is recommended in specific situations for patients with hypertrophic cardiomyopathy (HCM). The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines indications for heart transplantation include advanced heart disease and New York Heart Association (NYHA) functional class III or IV symptoms that are refractory to all other interventions.[22, 23] In addition, transplant referral for refractory symptoms does not require a reduced ejection fraction (EF), and heart transplantation is performed in the presence of preserved EF.[22, 23]

HCM patient outcome after heart transplant is not different from that of other patients with other heart diseases.[22, 23]

2011 ACCF/AHA recommendations

The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding heart transplantation in patients with HCM are summarized below.[22, 23]

Class I recommendations

Heart transplantion should not be considered in the setting of advanced heart failure (end stage) and nonobstructive HCM not otherwise amenable to other treatment intervention, in the presence of an ejection fraction (EF)  that is at or below 50% (or, occasionally, with preserved EF). (Level of evidence: B)

Pediatric heart transplant candidates include those with symptomatic HCM with a restrictive physiology who are not responsive to or appropriate candidates for other therapeutic interventions. (Level of evidence: C)

Precautions (class III recommendations)

To prevent harm, do not perform heart transplantation in mildy symptomatic patients of any age with HCM. (Level of evidence: C)

Atrial Fibrillation Management

Atrial fibrillation is an important complication of hypertrophic cardiomyopathy (HCM) that is diagnosed by electrocardiography (ECG) during an atrial fibrillation episode, on ambulatory Holter monitoring, or on an event monitor.[22, 23] This arrhythmia generally seen in patients with HCM who are older than 30 years. In addition to increasing age, risk factors for atrial fibrillation in the setting of HCM include congestive heart failure, left atrial function, diameter, and volume. Although patients with HCM and atrial fibrillation may be asymptomatic, there is an increased risk of heart failure, death, and stroke in this population.[22, 23]

2011 ACCF/AHA recommendations

Treatment for atrial fibrillation include symptom control and stroke prevention. The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding management of atrial fibrillation in patients with HCM are summarized below.[22, 23]

Class I recommendations

Use vitamin K antagonis (ie, warfarin, to an international normalized ratio [INR] of 2-3) for anticoagulation in patients with paroxysmal, persistent, or chronic atrial fibrillation AF and HCM. (Data are not available in the setting of HCM for anticoagulation with direct thrombin inhibitors such as dabigatran in reducing the risk of thromboembolism). (Level of evidence: C)

Control the ventricular rate in patients with HCM and atrial fibrillation who have rapid ventricular rates. High doses of beta antagonists and nondihydropyridine calcium channel blockers may need to be administered. (Level of evidence: C)

Class IIa recommendations

The ACCF/AHA indicates it is reasonable to use disopyramide (with ventricular rate–controlling agents) and amiodarone for atrial fibrillation in patients with HCM. (Level of evidence: B)

Radiofrequency ablation can be beneficial in the setting of HCM with refractory atrial fibrillation or patients unable to take antiarrhythmic agents. (Level of evidence: B)

Maze procedure with closure of the left atrial appendage is a reasonable intervention in patients with HCM and a histroy of atrial fibrillation. The procedure may be performed during septal myectomy or as an isolated procedure in selected patients. (Level of evidence: C)

Class IIb recommendations

Alternative antiarrhthmic agents for patients with HCM and atrial fibrillation include sotalol, dofetilide, and dronedarone, particularly in those with an implantable cardioverter defibrillator. (Level of evidence: C)

Pregnacy and Delivery Considerations

In general, women with HCM can safely undergo pregnancy and labor with minimal risks.[22, 23] However, preconception genetic counseling is advised, and it is essential that the expectant mothers receive careful prepregnancy and pregnancy evaluation and functional assessment. Cesarean delivery is usually not required.[22, 23]

If the patient's HCM is controlled with medical therapy, then such management should be continued with careful maternal-fetal monitoring. In setting of advanced disease (eg, progressive heart failure, severe diastolic dysfunction, ventricular tachycardia, supraventricular tachycardia, marked left ventricular outflow tract obstruction [LVOT]), management with a multidisciplinary team that includes a materal-fetal specialist and cardiologist is crucial.[22, 23]

Pillarisetti et al reported that predictors of improvement in left ventricular dysfunction in patients with peripartum cardiomyopathy appear to include postpartum diagnosis and white/Hispanic race.[35]

Data spanning 2 decades and 160,000 deliveries from an institutional review of pregnant women with hypertrophic cardiomyopathy showed a small number of completed pregnancies (23 completed in 14 patients) and no maternofetal deaths.[36] The overall morbidity was 26%, with a 13% incidence of peripartum congestive heart failure.[36]

2011 ACCF/AHA recommendations

The 2011 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines recommendations regarding management of pregnancy and/or delivery in women with HCM are summarized below.[22, 23]

Class I recommendations

Pregnancy is not contraindicated in asymptomatic women with HCM; perform a careful evaluation for pregnancy risks. Asymptomatic women or those whose symptoms are controlled with beta-blocking drugs should continue pharmacotherapy during their pregnancy, and close monitoring for fetal bradycardia or other complications is important. (Level of evidence: C)

Male and female patients with HCM should receive genetic counseling before planned conception. (Level of evidence: C)

Management by a high-risk obstetric team is essential for women with HCM and resting or provocable LVOT obstruction of 50 mm Hg or greater and/or cardic symptoms not controlled by medical therapy alone. (Level of evidence: C)

Class IIa recommendations

Management by an expert materal-fetal team is advised for women with HCM whose symptoms are controlled (mild to moderate). Such specialist care includes cardiovascular and prenatal monitoring. (Level of evidence: C)

Precautions (class III recommendations)

Women with advanced heart failure symptoms and HCM have an increased risk of  excess morbidity/mortality in pregnancy. (Level of evidence: C)

Occupational Considerations

Federal Motor Carrier Safety Administration recommendations

The Federal Motor Carrier Safety Administration (FMCSA) sets medical standards and guidelines for commerical motor vehicle drivers. Current guidelines state that individuals with hypertrophic cardiomyopathy (HCM) should not be certified to drive CMV. However, the Medical Expert Panel (MEP) recommends that the guidelines be changed to reflect the fact that not all individuals with HCM are at risk for sudden incapacitation or death. Specifically, the panel recommends that individuals who meet all the following criteria are at low risk and may be certified to drive[37] :

  • No history of cardiac arrest
  • No spontaneous sustained ventricular tachycardia (VT)
  • Normal exercise blood pressure (BP) (eg, no decrease in BP at maximal exercise)
  • No nonsustained VT
  • No family history or premature sudden death
  • No syncope
  • Has an left ventricular (LV) septum thickness of less than 30 mm

However, low-risk individuals must be closely monitored for changes in their risk status.[37]

Federal Aviation Administration standards

The Federal Aviation Administration (FAA) sets the criteria for aircraft pilots with medical conditions, including cardiovascular diseases.[38] Currently, HCM is incompatible with the highest grade aviation license for commercial pilots due to its unpredictable risk for impairment in the cockpit.[39, 40, 41]

Activity

Avoid strenuous exercise. Competitive-level sports should not be permitted if any of the following is present:

  • Significant outflow gradient

  • Significant ventricular or supraventricular arrhythmia

  • Marked LV hypertrophy

  • History of sudden death in relatives with hypertrophic cardiomyopathy (HCM)

  • Identified malignant genotype

  • Young age (< 30 years)

  • Abnormal blood pressure response to exercise

  • History of syncope, particularly in children

Although avoidance of intense physical exertion is probably appropriate, participation in noncompetitive-level recreational sports activities is not believed to be contraindicated.

Cardiovascular screening before participation in competitive sports appears to reduce the frequency of unexpected sudden death from HCM, although whether large-scale screening of athletes is administratively feasible or cost-effective remains to be determined.[42, 43]

Sudden death often occurs during exercise, but it also demonstrates a circadian distribution, with clustering of deaths in the morning and early evening.

 

Medication

Medication Summary

The purpose of pharmacologic therapy is to reduce the pressure gradient across the LV outflow tract by reducing the inotropic state of the left ventricle, improving compliance of the left ventricle, and reducing diastolic dysfunction. To date, only 1 pharmacologic agent, amiodarone (Cordarone), has been shown to reduce the incidence of arrhythmogenic sudden cardiac death.[44, 45]

Beta-Adrenergic Blocking Agents

Class Summary

These reduce the inotropic state of the left ventricle. They decrease diastolic dysfunction and increase LV compliance, thereby reducing the pressure gradient across LV outflow tract. Beta-adrenergic blocking agents decrease heart rate, thus lowering myocardial oxygen consumption and reducing the potential for myocardial ischemia.

Metoprolol (Lopressor, Toprol XL)

This is a first-line therapy in the treatment of obstructive and nonobstructive hypertrophic cardiomyopathy (HCM). Rarely, patients may require up to 200 mg orally twice daily to achieve the desired effect. The dose is titrated to a heart rate of between 50 and 60 bpm.

Atenolol (Tenormin)

Atenolol selectively blocks beta1 receptors, with little or no effect on beta2 types.

Sotalol (Betapace, Sorine)

This is a class III antiarrhythmic agent that blocks K+ channels, prolongs action potential duration, and lengthens the QT interval. Sotalol is a noncardiac selective beta-adrenergic blocker that may be helpful in the conversion of atrial fibrillation and flutter to normal rhythm. It may also suppress the recurrence of atrial fibrillation and flutter.

Propranolol (Inderal LA, InnoPran XL)

Propranolol is a class II antiarrhythmic nonselective beta-adrenergic receptor blocker with membrane-stabilizing activity that decreases the automaticity of contractions. The

dose is titrated to a heart rate of between 50 and 60 bpm.

Antiarrhythmics

Class Summary

These agents alter the electrophysiologic mechanisms responsible for arrhythmia.

Disopyramide (Norpace, Norpace CR)

Disopyramide decreases the inotropic state of the left ventricle. It decreases ventricular and supraventricular arrhythmias. The drug decreases diastolic dysfunction and increases LV compliance, thereby reducing the pressure gradient across the LV outflow tract. Disopyramide raises the threshold for atrial and ventricular ectopy.

Amiodarone (Cordarone, Pacerone)

Amiodarone is the only agent proven to reduce the incidence and risk of cardiac sudden death, with or without obstruction to LV outflow. It is very effective at converting atrial fibrillation and flutter to sinus rhythm and at suppressing the recurrence of these arrhythmias.

Calcium Channel Blockers

Class Summary

An alternative to beta blockers, calcium channel blockers decrease the inotropic state of the left ventricle, decrease the gradient across the LV outflow tract, decrease diastolic dysfunction, and increase diastolic filling of the left ventricle by improving LV diastolic relaxation. These agents may have a better effect on exercise performance.

Verapamil (Calan, Isoptin, Verelan)

During depolarization, verapamil inhibits calcium ions from entering slow channels or voltage-sensitive areas of the vascular smooth muscle and myocardium. The drug provides an alternative to beta-blocker therapy. It is useful in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

The use of short-acting calcium channel blockers is being discouraged because of numerous reports of adverse cardiac and hemodynamic events associated with their use, particularly in patients with known coronary artery disease.

Anticoagulants, Cardiovascular

Class Summary

Anticoagulants are used to prevent thromboembolic complications.

Warfarin (Coumadin, Jantoven)

Warfarin is a competitive, direct thrombin inhibitor. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby preventing thrombus development. It inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. Warfarin is indicated for the prevention of stroke and thromboembolism associated with nonvalvular atrial fibrillation.