Hypertrophic Obstructive Cardiomyopathy

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 a family history secondary to de novo mutations. HOCM results from a gene mutation that encodes for 1 of the 9 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 this 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

HOCM 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 depends on 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 the systolic anterior motion 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 in about 70% of patients, it can be brought about with provocative maneuvers. Most patients 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 reduced diameter.

History and Physical

A thorough history and physical should be performed. All patients should be asked about a family history of HOCM and 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 are frequently 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. The physical exam does not provide a definitive diagnosis but 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, 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 left ventricular outflow tract will decrease with an increase in preload (squatting) or 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 left ventricle outflow gradient and decreasing murmur intensity.
• Valsalva maneuver will decrease ventricular volume, increase the left ventricle outflow gradient, and increase murmur intensity.
• Beta-blockers will increase ventricular volume, decrease left ventricle outflow gradient, and decrease murmur intensity.

Evaluation

Lab studies should be normal, but brain natriuretic peptide may be elevated with severe disease. 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. An electrocardiogram may show left ventricular hypertrophy. It may also show arrhythmias such as atrial fibrillation or non-sustained ventricular tachycardia. However, electrocardiograms can frequently be normal. 2D echocardiography is the primary imaging modality used to diagnose HOCM. The echo has an 80% diagnostic accuracy for HOCM. Direct visualization and relatively accurate measurements of the septum and left ventricular wall sizes can be done. It will be able to show increased flow velocity along the left ventricular outflow tract. Color flow Doppler can show mitral valve regurgitation. Reduced left ventricle 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 left ventricular outflow tract is often obvious. Cardiac MRI is considered the gold standard for diagnosing left ventricle 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 accurately determine the degree of outflow tract obstruction, left ventricle anatomy, mitral valve regurgitation, and coronary artery patency. 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. The first line of medical treatment for symptomatic HOCM is beta blockers, though cardiac selective calcium channel blockers may be used. Angiotensin-converting enzyme inhibitors and nitrates should be avoided as these medications decrease afterload, worsening left ventricle outflow tract obstruction. [8][9][10][11] Surgical intervention is reserved for patients resistant to lifestyle and medical management or those with an 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.(B3)

Differential Diagnosis

The differential diagnosis for hypertrophic obstructive cardiomyopathy include the following:

• 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

The complications that can manifest with hypertrophic obstructive cardiomyopathy are as follows:

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