Hypertrophic cardiomyopathy: causes, symptoms, diagnosis, treatment

Hypertrophic cardiomyopathy is a congenital or acquired disorder characterized by marked ventricular myocardial hypertrophy with diastolic dysfunction but without increased afterload (in contrast to, for example, valvular aortic stenosis, coarctation of the aorta, systemic arterial hypertension). Symptoms include chest pain, dyspnea, syncope, and sudden death. A systolic murmur that increases with the Valsalva maneuver is usually heard in the obstructive hypertrophic type. Diagnosis is made by echocardiography. Treatment is with beta-blockers, verapamil, disopyramide, and sometimes chemical reduction or surgical removal of the outflow tract obstruction.

Hypertrophic cardiomyopathy (HCM) is a common cause of sudden death in young athletes. It can cause unexplained fainting spells and can only be diagnosed at autopsy.

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Causes of hypertrophic cardiomyopathy

Most cases of hypertrophic cardiomyopathy are inherited. At least 50 different mutations are known, inherited in an autosomal dominant pattern; spontaneous mutations are common. Probably 1 in 500 people are affected, and stenotypic expression is highly variable.

Myocardial pathology is characterized by disorientation of cells and myofibrils, although these manifestations are not specific for hypertrophic cardiomyopathy. In the most common variants, the superior portion of the interventricular septum below the aortic valve is markedly hypertrophied and thickened, with minimal or no hypertrophy of the posterior wall of the left ventricle (LV); this variant is called asymmetric septal hypertrophy. During systole, the septum thickens, and sometimes the anterior leaflet of the mitral valve, already maloriented due to the irregular shape of the ventricle, is sucked onto the septum by high-velocity blood flow (Venturi effect), further narrowing the outflow tract and reducing cardiac output. The resulting disorder may be called hypertrophic obstructive cardiomyopathy. Less commonly, hypertrophy of the midseptum results in an intracavitary gradient at the level of the papillary muscles. In both forms, the distal left ventricle may eventually become thin and dilated. Apical hypertrophy also occurs but does not impede outflow, although this variant may lead to obliteration of the apical left ventricle during systole.

Contractility is completely normal, resulting in a normal ejection fraction (EF). Later, EF increases because the ventricle has a small volume and empties almost completely to maintain cardiac output.

Hypertrophy results in a stiff, noncompliant chamber (usually the LV) that resists diastolic filling, elevating end-diastolic pressure and thus increasing pulmonary venous pressure. As filling resistance increases, cardiac output decreases, an effect that is exacerbated by any outflow tract gradient. Because tachycardia results in decreased filling time, symptoms tend to occur primarily during exercise or with tachyarrhythmias.

Coronary blood flow may be impaired, causing angina, syncope, or arrhythmias in the absence of coronary artery disease. Blood flow may be impaired because the ratio of capillary density to cardiomyocytes is abnormal (capillary/myocyte imbalance) or the lumen diameter of the intramural coronary arteries is narrowed due to intimal and media hyperplasia and hypertrophy. In addition, peripheral vascular resistance and aortic root diastolic pressure decrease with exercise, resulting in decreased coronary artery perfusion pressure.

In some cases, myocytes gradually die, probably because the imbalance at the capillary/myocyte level causes chronic widespread ischemia. As myocytes die, they are replaced by widespread fibrosis. In this case, the hypertrophied ventricle with diastolic dysfunction gradually dilates, and systolic dysfunction develops.

Infective endocarditis may complicate hypertrophic cardiomyopathy due to mitral valve abnormality and rapid outflow of blood during early systole. Atrioventricular block is sometimes a late complication.

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Symptoms of hypertrophic cardiomyopathy

Symptoms typically appear between the ages of 20 and 40 and are exertional. They include chest pain (usually resembling typical angina), dyspnea, palpitations, and syncope. Patients may have one or more of these symptoms. Syncope usually occurs without warning during exercise due to undiagnosed ventricular or atrial arrhythmia and is a marker of high risk of sudden death. In hypertrophic cardiomyopathy, sudden death is thought to be due to ventricular tachycardia or fibrillation. Since systolic function is preserved, patients rarely complain of fatigue.

Blood pressure and heart rate are usually normal, and symptoms of increased venous pressure are rare. With outflow tract obstruction, the carotid pulse has a sharp rise, a split peak, and a rapid decline. The apical impulse may be pronounced due to left ventricular hypertrophy. A fourth heart sound (S4) is often present _, associated with a powerful atrial contraction against a background of a poorly compliant left ventricle in late diastole.

Septal hypertrophy produces an ejection systolic murmur that does not radiate to the neck and may be heard at the left sternal border in the third or fourth intercostal space. A mitral regurgitation murmur due to a change in the configuration of the mitral valve may be heard at the apex of the heart. With RV outflow tract narrowing, an ejection systolic murmur is sometimes heard at the second intercostal space at the left sternal border. The left ventricular outflow tract ejection murmur of hypertrophic cardiomyopathy may be increased by the Valsalva maneuver (which decreases venous return and left ventricular diastolic volume), by lowering aortic pressure (eg, with nitroglycerin), or during contraction after an extrasystole (which increases the outflow tract pressure gradient). Hand squeezing increases aortic pressure, thus decreasing the murmur.

Diagnosis of hypertrophic cardiomyopathy

A presumptive diagnosis is made based on the typical murmur and symptoms. Unexplained syncope in young athletes should always prompt an investigation to exclude HCM. This pathology must be distinguished from aortic stenosis and ischemic heart disease, which may be accompanied by similar symptoms.

An ECG and 2D echocardiography (the best noninvasive test to confirm the diagnosis) are performed. Chest X-rays are often done but are usually unremarkable because the ventricles are not dilated (although the left atrium may be enlarged). Patients with syncope or persistent arrhythmias should be evaluated in a hospital setting. Exercise testing and Holter monitoring are often helpful in high-risk patients, although diagnosis is difficult in these patients.

The ECG usually shows signs of left ventricular hypertrophy (eg, an S wave in lead V plus an R wave in lead V or V > 35 mm). Very deep septal O waves in leads I, aVL, V, and V are often seen with asymmetric septal hypertrophy. In HCM, a QRS complex is sometimes found in leads V3 and V4, simulating a previous MI. The waves are usually abnormal, most often deep symmetrical inverted waves are present in leads I, aVL, V5, and V6. ST segment depression in these leads is also common. The P wave is usually wide, split in leads II, III, and aVF, and biphasic in leads V and V, indicating left atrial hypertrophy. There is an increased risk of preexcitation phenomenon in Wolff-Parkinson-White syndrome, which leads to arrhythmia.

Two-dimensional Doppler echocardiography helps differentiate forms of cardiomyopathy and determine the degree of left ventricular outflow tract obstruction, including the pressure gradient and localization of the stenotic segment. This study is especially important for monitoring the effectiveness of drug or surgical treatment. In cases of severe outflow tract obstruction, aortic valve closure in mid-systole is sometimes noted.

Cardiac catheterization is usually performed only when invasive treatment is planned. Coronary arteries usually do not show significant stenosis, but metabolic studies may reveal myocardial ischemia due to intramural narrowing of the arterial lumen, imbalance at the capillary/myocyte level, or abnormal ventricular wall tension. Elderly patients may also have coronary artery disease.

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Prognosis and treatment of hypertrophic cardiomyopathy

Overall, the annual mortality rate is 1–3% in adults and is higher in children. Mortality is inversely proportional to the age at onset of symptoms and is highest in patients with frequent sustained ventricular tachycardia or syncope and in those resuscitated from sudden cardiac arrest. The prognosis is worse in younger patients with a family history of sudden death and in patients over 45 years of age with angina or dyspnea on exertion. Death is usually sudden, and sudden death is the most common complication. Chronic heart failure is less common. Genetic counseling is indicated in patients with asymmetric septal hypertrophy that developed during the growth period of puberty.

Treatment is primarily aimed at pathological diastolic relaxation. β-Adrenergic blockers and heart rate-slowing calcium channel blockers with a slight vasodilatory effect (e.g., verapamil) as monotherapy or in combination form the basis of therapy. By reducing myocardial contractility, these drugs dilate the heart. By slowing the heart rate, they prolong the diastolic filling period. Both effects reduce outflow tract obstruction, thereby improving ventricular diastolic function. In severe cases, disopyramide can be added, given its negative inotropic effect.

Drugs that reduce preload (eg, nitrates, diuretics, ACE inhibitors, angiotensin II receptor blockers) reduce chamber size and worsen symptoms of hypertrophic cardiomyopathy. Vasodilators increase the outflow tract gradient and cause reflex tachycardia, which subsequently worsens ventricular diastolic function. Inotropic drugs (eg, digitalis glycosides, catecholamines) worsen outflow tract obstruction without reducing high end-diastolic pressure, which can cause arrhythmias.

In cases of syncope, sudden cardiac arrest, or if arrhythmia is confirmed by ECG or 24-hour ambulatory monitoring, implantation of a cardioverter-defibrillator or antiarrhythmic therapy should be considered. Antibiotic prophylaxis of infective endocarditis is recommended for patients with hypertrophic cardiomyopathy. Participation in competitive sports is contraindicated, since many cases of sudden death occur during increased exertion.

Treatment during the expansion and congestion phase of hypertrophic cardiomyopathy is the same as treatment of hypertrophic cardiomyopathy with predominant systolic dysfunction.

If septal hypertrophy and outflow tract obstruction cause significant symptoms despite medical treatment, surgery is necessary. Catheter ablation with ethyl alcohol is not always effective, but is becoming more widely used. Surgical septal myotomy or myomectomy reduces symptoms more reliably but does not improve survival.