Treating Left Ventricular Outflow Tract Obstruction with Mavacamten

Hypertrophic cardiomyopathy (HCM) is the most common type of cardiomyopathy (heart muscle disease), characterized by unexplained thickening of the heart muscle, mainly at the left heart. It is usually caused by a mutation in cardiac genes that control the heart muscle’s motor unit (sarcomere).

How does a normal sarcomere contraction work?

The sarcomere has a ‘thick filament’ called myosin and a ‘thin filament’ called actin, as shown below. During heart muscle contraction, the myosin heads cross-link with actin.

Myosin heads then undergo shape changes that slide the muscle fibres, producing a power stroke.

The myosin heads subsequently detach from the actin to be ready to cross-link again with actin for the next contraction.

Abnormal sarcomere function

In HCM, abnormalities in the sarcomeric genes cause excessive linkages between actin and myosin, increasing the power stroke during muscular contraction. This increment in heart muscle contractility contributes to a common complication of HCM, namely left ventricular outflow tract (LVOT) obstruction.

In LVOT obstruction, the left heart faces resistance to eject blood out. LVOT obstruction can happen in up to 70% of HCM patients. The symptoms of LVOT obstruction are shortness of breath and chest discomfort, usually during physical activities. Uncommonly, fainting or near fainting may occur.

Treatment

Treatment of LVOT obstruction would include lifestyle modification, medications and occasionally surgery. Traditional medicines for LVOT obstruction include beta-blockers (e.g. bisoprolol, metoprolol, etc.), calcium channel blockers (e.g. verapamil, diltiazem) and disopyramide. These medications have effects not only on the heart but also on other organ systems of the body, causing unpleasant side effects and reduced tolerability.

Recently, a new medication, Mavacamten, a first-in-class molecule, is available to treat LVOT obstruction. It reduces the myosin-actin cross-linkages, correcting the excessive contractility of the heart muscle that contributes to LVOT obstruction. Mavacamten is effective and well-tolerated, with no systemic side effects of the traditional medications.

Mavacamten is available in our clinic. Talk to us to understand HCM more and treatment options that are available for HCM.

Dr Tang Hak Chiaw

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