Continuing Education Activity

Hypertrophic obstructive cardiomyopathy (HOCM), historically referred to as idiopathic hypertrophic subaortic stenosis, is a relatively common disorder. HOCM is a significant cause of sudden cardiac death in young people, including well-trained athletes, and affects men and women equally across all races. In most patients, it results from asymmetric septal hypertrophy causing outflow obstruction of the left ventricle. It is difficult to diagnose and presents a challenge to medical health professionals in evaluating at-risk athletes. This activity reviews the evaluation and management of hypertrophic obstructive cardiomyopathy and highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance outcomes for affected patients.

Objectives:

• Discuss the recommended management of hypertrophic obstructive cardiomyopathy.
• Outline the typical presentation for a patient with hypertrophic obstructive cardiomyopathy.
• Review the pathophysiology of hypertrophic obstructive cardiomyopathy.
• Explain the interprofessional team strategies for improving care coordination and communication regarding the management of patients with hypertrophic obstructive cardiomyopathy.

Introduction

Hypertrophic obstructive cardiomyopathy (HOCM) is a relatively common disorder. Historically, it has been referred to as idiopathic hypertrophic subaortic stenosis.  HOCM is a significant cause of sudden cardiac death in young people, including well-trained athletes, affecting men and women equally across all races.  In most patients, it results from asymmetric septal hypertrophy causing outflow obstruction of the left ventricle.  It is difficult to diagnose and presents a challenge to medical health professionals in evaluating at-risk athletes.  Unfortunately, hypertrophic obstructive cardiomyopathy is often not diagnosed until a significant cardiac event has occurred.[1][2][3][4]

The hypertrophy can occur in any segment of the left ventricle but is most common in the interventricular septum. This often results in obstruction of blood flow through the left ventricular outflow tract. HOCM is a genetic disorder. Defects in several genes have been identified that result in septal hypertrophy. The condition is usually asymptomatic in children but may first present with sudden death in teenagers and adolescents.

Etiology

The familial form of HOCM is an autosomal dominant genetically transmitted disorder.  It is the most common genetically transmitted cardiomyopathy.  It can also occur in individuals without family history secondary to de novo mutations. HOCM results from a mutation in genes that encode for one of the nine sarcomere proteins, such as B-myosin heavy chain, troponin, actin, and titin. The mutations cause structural abnormalities in myofibril and myocytes that have the potential to lead to abnormal force generation and conduction abnormalities. The consequences of which are a phenotype for asymmetric left ventricular hypertrophy in the absence of other causes.  [5][6][7]

Other causes of HOCM include:

1. Heightened sympathetic stimulation due to excess catecholamine secretion or decreased uptake
2. Abnormally thickened coronary arteries which may not dilate normally. This may lead to ongoing myocardial ischemia, that eventually leads to ventricular fibrosis and compensatory hypertrophy
3. Abnormal microcirculation that prevents the normal contractile function of the myofibrils

Epidemiology

Hypertrophic obstructive cardiomyopathy occurs in men and women with equal distribution across all races.  Females tend to be more symptomatic causing more disability and present at a younger age.  A 1995 study by Maron et. Al. concluded that it occurs at a rate of 1:500 in the general adult population. In the United States alone, there are fewer than 100 deaths per year due to HOCM at a rate of 1:220,000 athletes.

Most patients present in the second/third decade of life. However, some adults may present between the fourth and sixth decades of life.

Pathophysiology

HOCM can be classified as obstructive or non-obstructive.  There is some degree of asymmetric left ventricular hypertrophy.   The degree of obstruction and clinical presentation is dependent upon the extent of hypertrophy.  It most commonly affects the ventricular septum (about 2/3 of patients), although any portion of the left ventricle can be affected. 

Dynamic outflow obstruction in HOCM is due to systolic anterior motion(SAM) of the anterior leaflet of the mitral valve. This is due to impingement of the mitral valve leaflets on the hypertrophied basal septum.  The outflow tract obstruction is dynamic and caused by a pressure gradient which pulls the anterior leaflet of the mitral valve anteriorly further leading to outflow tract obstruction. The degree of obstruction is dependent upon contractility and loading conditions.  In 25% of patients, the obstruction can exist at rest, but about 70% of patients can be brought about with provocative maneuvers. 

Most patient’s with HOCM have an abnormal diastolic function. This increases left ventricular pressures impairing ventricular filling which further exacerbates obstruction.  Because the coronary vessels are filled during diastole in combination with outflow tract obstruction and ventricular stiffness, there is an increased risk for myocardial ischemia. This may be responsible for ventricular arrhythmias and sudden death.  In severe cases, this can occur at rest. More commonly, it occurs with provocative maneuvers such as exercise during increased myocardial demand.

Histopathology

Histology may reveal the disorganization of the muscle fibers, cell to cell disarray and gross disorganization of the architecture. Fibrosis may be evident. The coronary arteries may be intramural and have a reduction in the diameter.

History and Physical

A thorough history and physical should be performed.  All patients should be asked about family history of HOCM and of sudden cardiac death. A majority of patients are asymptomatic.  Dyspnea is the most common complaint among symptomatic patients.  Patients may also complain of presyncope, syncope, angina, palpitations (secondary to arrhythmia), or dizziness.  Symptoms will frequently be exacerbated by exertion. Severe cases will present like congestive heart failure with paroxysmal nocturnal dyspnea, leg edema, and orthopnea.  The most devastating presentation is sudden cardiac death.

Physical Exam will not provide a definitive diagnosis, but it should provide clues to increase clinical suspicion.  Patients may present with a jugular venous pulse with prominent A wave, S4 heart sound, split-second heart sound (may paradoxically split in severe outflow tract obstruction), double carotid pulse, systolic ejection crescendo-decrescendo murmur, laterally displaced apical precordial impulse that may be abnormal forceful or enlarged, and/or a holosystolic murmur at the apex and axilla of mitral regurgitation with systolic anterior wall motion.  The lung exam should be normal.    

The murmur and the gradient across the LVOT will decrease with an increase in preload (Squatting)  or an increase in afterload (handgrip). In addition, the gradient and the murmur will increase with a decrease in preload (Valsalva maneuver, diuretics, standing).

• Certain maneuvers can affect murmurs auscultated in HOCM.

• Handgrip will increase ventricular volume decreasing LV outflow gradient and decrease murmur intensity.

• Valsalva maneuver will decrease ventricular volume increasing LV outflow gradient and increase murmur intensity.

• Beta-blockers will increase ventricular volume decreasing LV outflow gradient and decrease murmur intensity.

Evaluation

Lab studies should be normal, but with severe disease, BNP may be elevated.  Genetic testing is available and diagnostic but is reserved for patients with significant family histories or those who exhibit clear symptoms. The American Heart Association is currently opposed to routine screening for genetic markers.

A chest x-ray may be normal but left ventricular hypertrophy may be seen.

EKG may show LVH.  It may also show arrhythmias such as atrial fibrillation or non-sustained v-tach.  EKG can frequently be normal.

2D-echocardiography is the primary imaging modality to make the diagnosis of HCM. The echo has an 80% diagnostic accuracy for HOCM. There can be direct visualization and relatively accurate measurements of the septum and left ventricular wall sizes.  It will be able to show increased flow velocity along the left ventricular outflow tract. Color flow Doppler can show mitral valve regurgitation.  Reduced LV compliance can be seen in diastolic dysfunction. The key features of HOCM include the asymmetric septal wall thickness (more than 15 mm) and systolic anterior motion of the anterior mitral valve leaflet. The posterior septal wall is usually much thicker than the anterior septal wall. The narrowing of the LVOT is often obvious.

Cardiac MRI is considered the gold standard for diagnosis of LV wall properties and should be performed in patients suspected of having HOCM with a normal or inconclusive echocardiogram.

Cardiac catheterization is not required for diagnosis but may be performed to determine accurately the degree of outflow tract obstruction, LV anatomy, the degree of mitral valve regurgitation, and the patency of the coronary arteries.

Radionuclide imaging may reveal reversible defects in the absence of coronary artery disease.

Treatment / Management

Treatment is based on the severity of symptoms.  Mild disease is treated with lifestyle modifications.  Patients should be strongly advised to avoid strenuous exercise and heavy lifting.  First lime medical treatment for symptomatic HOCM is beta blockers though cardiac selective calcium channel blockers may be used. ACE inhibitors and nitrates should be avoided as these medications decrease afterload which would lead to worsening LV outflow tract obstruction.  [8][9][10][11]

Surgical intervention is reserved for patients who are resistant to lifestyle and medical management or those who have outflow gradient of 50mmhg or more. Septal myectomy is the surgical treatment of choice in young healthy patients.  Alcohol septal ablation is a newer percutaneous technique usually limited to older patients for whom an open procedure would be considered risky.

Differential Diagnosis

• Aortic valve stenosis
• Restrictive cardiomyopathy
• Pericardial tamponade

Prognosis

Mortality rates for HOCM have improved but still, range from 1-6%. Sudden death is the most common cause of death in young people. Studies show that midventricular obstruction is associated with a high risk of apical aneurysm formation, cardiac symptoms, and sudden death compared to patients who did not have the midventricular obstruction.

Death is often sudden and typically associated with a sporting activity. Screening of first degree relatives is now done to identify individuals at high risk for death. Patients with HOCM may develop a variety of atrial and ventricular arrhythmias. Heart failure is likely in patients with severe diastolic dysfunction. The condition is progressive and eventually, all patients will develop symptoms.

Complications

• Ventricular arrhythmias
• Congestive heart failure
• Infective endocarditis of the mitral valve
• Atrial fibrillation
• Embolic phenomenon
• Sudden death

Enhancing Healthcare Team Outcomes

The diagnosis and management of HOCM is with an interprofessional team that consists of a cardiologist, electrophysiologist, cardiac surgeon and an internist. The primary care provider and nurse practitioner usually play a role in follow up after treatment. The treatment of HOCM is based on the severity of symptoms.  Mild disease is treated with lifestyle modifications.  Patients should be strongly advised to avoid strenuous exercise and heavy lifting.  First lime medical treatment for symptomatic HOCM is beta blockers though cardiac selective calcium channel blockers may be used. ACE inhibitors and nitrates should be avoided as these medications decrease afterload which would lead to worsening LV outflow tract obstruction. The pharmacist must educate the patient on the importance of medication compliance.

Surgical intervention is reserved for patients who are resistant to lifestyle and medical management or those who have outflow gradient of 50mmhg or more. Septal myectomy is the surgical treatment of choice in young healthy patients.  Alcohol septal ablation is a newer percutaneous technique usually limited to older patients for whom an open procedure would be considered risky. The outlook for patients are treated is good but those who fail to comply with medical or surgical therapy have a very high risk of sudden death. Because the disorder also runs in families, siblings and other family members should be screened for the disorder. [6][12][13](level V)