Hypertrophic cardiomyopathy (HCM) is a congenital or acquired disorder characterized by marked ventricular hypertrophy with diastolic dysfunction but without increased afterload (eg, due to valvular aortic stenosis, coarctation of the aorta, systemic hypertension). Symptoms include dyspnea, chest pain, syncope, and sudden death. A systolic murmur, increased by Valsalva maneuver, is typically present in the hypertrophic obstructive type. Diagnosis is by echocardiography or cardiac MRI. Treatment is with beta-blockers, verapamil, disopyramide, and sometimes chemical reduction or surgical removal of outflow tract obstruction.
(See also Overview of Cardiomyopathies.)
Hypertrophic cardiomyopathy is a common cause of sudden death in young athletes. It may cause unexplained syncope and may not be diagnosed before autopsy.
Most cases of hypertrophic cardiomyopathy are inherited. At least 1,500 different mutations that are inherited in an autosomally dominant pattern have been identified; spontaneous mutations can also occur. At least 1 in 500 people are affected; phenotypic expression varies markedly.
The myocardium is abnormal with cellular and myofibrillar disarray, although this finding is not specific for hypertrophic cardiomyopathy.
In the most common phenotype, the anterior septum and contiguous anterior free wall below the aortic valve are markedly hypertrophied and thickened, with little or no hypertrophy of the left ventricular (LV) posterior wall. Sometimes isolated apical hypertrophy occurs; however, virtually any asymmetric pattern of left ventricular hypertrophy can be observed, and in a small minority of patients even symmetric hypertrophy has been noted.
About two thirds of patients exhibit obstructive physiology at rest or during exercise. Obstruction is the result of mechanical impedance to LV outflow during systole due to systolic anterior motion (SAM) of the mitral valve. During this process (SAM), the mitral valve and valve apparatus are sucked into the LV outflow tract by a Venturi effect of high-velocity blood flow, resulting in obstruction of flow and decrease in cardiac output. Mitral regurgitation can also occur as the result of distortion of leaflet motion by SAM of the mitral valve. This obstruction and valvular regurgitation contribute to the development of symptoms related to heart failure. Less commonly, midventricular hypertrophy leads to an intracavitary gradient at the papillary muscle level.
Contractility is grossly normal, resulting in a normal ejection fraction (EF). Later, EF is elevated because the ventricle has a small volume and empties nearly completely to maintain cardiac output.
Hypertrophy results in a stiff, noncompliant chamber (usually the left ventricle) that resists diastolic filling, elevating end-diastolic pressure and thus increasing pulmonary venous pressure. As resistance to filling increases, cardiac output decreases, an effect worsened by any outflow tract gradient present. Because tachycardia allows less time for filling, symptoms tend to appear mainly during exercise or tachyarrhythmias.
Coronary blood flow may be impaired, causing angina pectoris, syncope, or arrhythmias in the absence of epicardial coronary artery disease (CAD). Flow may be impaired because capillary density relative to myocyte size is inadequate (capillary/myocyte imbalance) or lumen diameter of intramyocardial coronary arteries is narrowed by intimal and medial hyperplasia and hypertrophy. A supply-demand mismatch also may be present due to increased oxygen demand caused by the hypertrophy and adverse loading conditions.
In some cases, myocytes gradually die, probably because capillary/myocyte imbalance causes chronic diffuse ischemia. As myocytes die, they are replaced by diffuse fibrosis. Then, the hypertrophied ventricle with diastolic dysfunction gradually dilates and systolic dysfunction develops.
Infective endocarditis can complicate hypertrophic cardiomyopathy because of the mitral valve abnormality and because of rapid blood flow through the outflow tract during early systole. Atrioventricular block is sometimes a late complication.
Typically, symptoms appear between ages 20 and 40 and are exertional, but symptoms may be highly variable. They include dyspnea, chest pain (usually resembling typical angina), palpitations, and syncope. Because systolic function is preserved, fatigability is seldom reported. The abnormal diastolic function is responsible for most symptoms. In patients with outflow tract obstruction, differentiation of symptoms due to the obstruction versus those caused by abnormal diastolic function can be difficult.
Syncope may occur during exertion either because outflow obstruction worsens with increased contractility or because of nonsustained ventricular or atrial arrhythmia. Syncope is a marker of increased risk of sudden death, which is thought to result from ventricular tachycardia or fibrillation.
Blood pressure and heart rate are usually normal, and signs of increased venous pressure are rare. When the outflow tract is obstructed, the carotid pulse has a brisk upstroke, bifid peak, and rapid downstroke. The apex beat may have a sustained thrust due to LV hypertrophy. A 4th heart sound (S4) is often present and is associated with a forceful atrial contraction against a poorly compliant LV in late diastole.
In patients with the obstructive form of hypertrophic cardiomyopathy, a systolic ejection-type murmur can be heard that does not radiate to the neck. This murmur is heard best at the left sternal edge in the 3rd or 4th intercostal space. A mitral regurgitation murmur due to distortion of the mitral apparatus may be heard at the apex. The left ventricular outflow ejection murmur of hypertrophic cardiomyopathy can be increased by a Valsalva maneuver (which reduces venous return and LV diastolic volume), measures to lower aortic pressure (eg, nitroglycerin), or a postextrasystolic contraction (which increases the outflow tract pressure gradient). Handgrip increases aortic pressure, thereby reducing the murmur’s intensity.
Diagnosis is suspected based on a typical murmur and symptoms. Suspicion is increased if the patient has a history of unexplained syncope or a family history of unexplained sudden death. Unexplained syncope in young athletes should always raise suspicion. Hypertrophic cardiomyopathy must be distinguished from aortic stenosis and coronary artery disease, which cause similar symptoms.
ECG and 2-dimensional echocardiography and/or MRI (the best noninvasive confirmatory tests) are done. Chest x-ray is often done but is usually normal because the ventricles are not dilated (although the left atrium may be enlarged). Patients with syncope or sustained arrhythmias should be evaluated as inpatients. Exercise testing and 24-h ambulatory monitoring may be helpful for patients considered at high risk, although accurately identifying such patients is difficult.
The ECG usually shows voltage criteria for LV hypertrophy (eg, S wave in lead V1 plus R wave in lead V5 or V6 > 35 mm). Very deep septal Q waves in leads I, aVL, V5, and V6 are often present with asymmetric septal hypertrophy; hypertrophic cardiomyopathy sometimes produces a QRS complex in V1 and V2, simulating previous septal infarction. T waves are usually abnormal; the most common finding is deep symmetric T-wave inversion in leads I, aVL, V5, and V6. ST-segment depression in the same leads is common (particularly in the apical obliterative form). The P wave is often broad and notched in leads II, III, and aVF, with a biphasic P wave in leads V1 and V2, indicating left atrial hypertrophy. Incidence of preexcitation phenomenon of the Wolff-Parkinson-White syndrome type, which may cause palpitations, is increased. Bundle branch block is common.
Two-dimensional Doppler echocardiography can differentiate the forms of cardiomyopathy (see Figure: Forms of cardiomyopathy.) and quantify the severity of hypertrophy and degree of outflow tract obstruction . These measurements are particularly useful for monitoring the effect of medical or surgical treatment. Midsystolic closure of the aortic valve sometimes occurs when outflow tract obstruction is severe.
Cardiac catheterization is usually done only when invasive therapy is considered. Usually, no significant stenoses are present in the coronary arteries, but elderly patients may have coexisting CAD.
Genetic markers do not influence treatment or identify high-risk individuals. However, genetic testing may be of benefit in screening family members.
Overall, annual mortality is about 1% for adults but is higher for children. Death is usually sudden, and sudden death is the most common sequelae; chronic heart failure occurs less often. A higher risk of sudden cardiac death is predicted by the presence of the following risk factors:
Family history of sudden cardiac death due to hypertrophic cardiomyopathy
Unexplained recent syncope
Multiple repetitive non-sustained ventricular tachycardia (on ambulatory ECG)
Hypotensive or attenuated blood pressure response to exercise
Massive left-ventricular hypertrophy (thickness ≥ 30 mm)
Extensive and diffuse late gadolinium enhancement on MRI
Treatment is based on the phenotype. Patients without obstruction generally have a stable clinical course without significant symptoms, although some experience heart failure symptoms due to diastolic dysfunction. Beta-blockers and heart rate-limiting calcium channel blockers with a lower arterial dilation capacity (usually verapamil), alone or combined, are the mainstays. By slowing the heart rate, they prolong the diastolic filling period, which may increase left ventricular filling in patients with diastolic dysfunction. Long-term efficacy of such therapy, however, has not been proven.
In patients with the obstructive phenotype, in addition to attempts at improving diastolic function, treatment is directed at reducing the outflow tract gradient. Non-dihydropyridine calcium channel blockers, beta-blockers, and disopyramide reduce the outflow tract gradient through their negative inotropic effects. Disopyramide appears to be most effective for patients with a resting gradient whereas beta-blockers are best at blunting the gradient that occurs during exercise.
Patients who continue to experience symptoms related to significant outflow tract gradients (≥ 50 mm Hg) despite medical therapy are candidates for invasive treatment. When done at an experienced center, surgical myectomy has a low operative mortality with excellent outcomes, making it the preferred therapy in such patients. Percutaneous catheter alcohol septal ablation is an alternative to surgery in elderly patients and others who are at high surgical risk.
Drugs that reduce preload (eg, nitrates, diuretics, ACE inhibitors, angiotensin II receptor blockers) decrease chamber size and worsen symptoms and signs. Vasodilators increase the outflow tract gradient and cause a reflex tachycardia that further worsens ventricular diastolic function. Inotropic drugs (eg, digitalis glycosides, catecholamines) worsen outflow tract obstruction, do not relieve the high end-diastolic pressure, and may induce arrhythmias.
If syncope or sudden cardiac arrest has occurred or if ventricular arrhythmia is confirmed by ECG or 24-h ambulatory monitoring, an implantable cardioverter-defibrillator (ICD) should usually be placed. Controversy exists regarding the need to place a defibrillator in patients without syncope, sudden cardiac arrest, or ventricular arrhythmias. It is generally believed that ICD insertion should be considered in patients with high-risk features, which include a family history of premature sudden cardiac arrest, LV wall thickness > 3 cm, abnormal blood pressure response on exercise treadmill testing (fall in systolic pressure of > 10 mm Hg), left ventricular outflow tract obstructive gradient of > 50 mm Hg, or delayed enhancement on cardiac MR imaging. Competitive sports should be avoided because many sudden deaths occur during increased exertion.
Treatment of the dilated congestive phase of hypertrophic cardiomyopathy is the same as that of dilated cardiomyopathy with predominant systolic dysfunction.
Genetic counseling is appropriate for patients with asymmetric septal hypertrophy.
Hypertrophic cardiomyopathy is usually due to one of numerous genetic mutations that cause various types of ventricular hypertrophy that restrict filling (ie, cause diastolic dysfunction) and sometimes obstruct LV outflow.
Coronary blood flow may be impaired even in the absence of coronary artery atherosclerosis because capillary density is inadequate and the intramyocardial coronary arteries are narrowed by intimal and medial hyperplasia and hypertrophy
At a young age, patients may have chest pain, dyspnea, palpitations, syncope, and sometimes sudden death, typically triggered by exertion.
Echocardiography is done, but, if available, MRI best shows the abnormal myocardium.
Usebeta-blockers and/or rate-limiting calcium channel blockers (usually verapamil) to decrease myocardial contractility and slow the heart rate and thus prolong diastolic filling and decrease outflow obstruction.
Avoid nitrates and other drugs that decrease preload (eg, diuretics, ACE inhibitors, angiotensin II receptor blockers) because these decrease LV size and worsen LV function.
Place an implantable cardioverter-defibrillator for patients with syncope or sudden cardiac arrest.
Do surgical myomectomy or alcohol septal ablation in patients with symptoms despite medical therapy.