Hypertrophic cardiomyopathy (HCM) is a genetic (autosomal dominant) heart muscle disease caused by a mutation in sarcomere protein genes which encodes for elements of the contractile machinery of the heart. It is characterized by an increase in left ventricular wall thickness (hypertrophy) which causes left ventricular outflow obstruction, diastolic dysfunction, myocardial ischemia, and mitral regurgitation.
These structural and function abnormalities can produce fatigue, dyspnea, chest pain, palpitations, and syncope. Sudden cardiac death can represent the most devastating presenting manifestation, especially in young athletes.
Familial Hypertrophic cardiomyopathy occurs as an autosomal dominant Mendelian-Inherited disorder in approximately 50% of cases. A mutation in the sarcomere protein gene encoding for contractile elements of the heart has been found, with 6 different genes on at least 4 chromosomes being associated with HCM. More than 50 different mutations have been identified. The phenotypic expression may vary according to the mutation involved, with a variability of symptoms and degree of severity of the hypertrophy expressed. Recent data has associated abnormal myocardial calcium kinetics to the cause of inappropriate myocardial hypertrophy and specific features of HCM, especially in patients with diastolic functional abnormalities.
The prevalence of HCM in the general population around the world is 0.2% (1 in 500 adults), determined from echocardiographic studies. The morphologic evidence is found in approximately 25% of first-degree relatives of patients with HCM. Newer genetic testing has been developed and can be used to identify asymptomatic family members with same sarcomere mutation. HCM is more common in males than females, however, since the condition is autosomal dominant, genetic inheritance does not follow sex predilection. The most common presentation is in the third decade of life but may be present at any age, from newborns to elderly patients.
Ventricular hypertrophy results in a dynamic pressure gradient across the left ventricular outflow tract (LVOT), which is associated with further narrowing during systole. During this cardiac cycle, the mitral valve is pulled towards the septum by several proposed mechanisms: contraction of the papillary muscles, abnormal location in the outflow tract, and low pressure that occurs as blood is ejected at high velocity through a narrowed outflow tract (Venturi effect).
Histology usually reveals myocardial hypertrophy with a gross disarray of the myofibrils and disorganization of the muscle architecture.
There are visible fibrous scars and abnormal internal coronary vessels.
The histological abnormality is most often seen in the ventricular septum.
The most common presenting symptom of hypertrophic cardiomyopathy is dyspnea. Patients also can develop syncope, palpitations, angina, orthopnea, paroxysmal nocturnal dyspnea, dizziness, congestive heart failure, and sudden cardiac death. The latter represents the most devastating presenting symptom.
Physical examination findings are characterized by a double apical impulse due to forceful left atrial contraction against a highly noncompliant left ventricle, normal s1 and split s2, s3 due to decompensated heart failure, prominent "a wave" of jugular venous pressure, laterally displaced apical impulse, and double carotid pulse.
A systolic ejection murmur is present as follows: diminished intensity with increase preload (squatting) or afterload (handgrip) and increased intensity with a decrease in preload (Valsalva maneuver, standing), and with any decrease in afterload (vasodilator administration).
All patients should have a comprehensive cardiac history and physical examination. An electrocardiogram (ECG) and cardiac imaging to identify left ventricular hypertrophy should be performed in all patients.
Some patients may also require the following:
Cardiac catheterization: Determines cardiac hemodynamic, the degree of left ventricular outflow obstruction, and anatomy of the coronary vessels.
Electrophysiological studies: Determine the origin of the arrhythmias.
Treatment strategies for HCM are based upon observational data and clinical experience since no large randomized trials have been performed. Pharmacological therapy is the first-line approach to symptomatic HCH. The best initial medications include negative inotropic agents, including beta blockers, nondihydropyridine calcium channel blockers (verapamil), and disopyramide.
Surgical therapeutic options include the following:
A heart transplant is not the first treatment option and usually recommended only in patients who have failed all medical and surgical treatments.
Left ventricular myomectomy
Mitral valve replacement
Permanent pacemaker implantation
Placement of an implantable cardioverter defibrillator is an option in patients with ventricular fibrillation who do not want lifelong medical therapy.