Cardiac myosin inhibitors are a new class of medications designed to treat specific heart muscle conditions. They offer a targeted approach by directly influencing how the heart muscle contracts. This development marks a significant advancement in treating heart disorders, moving beyond symptomatic relief to address underlying mechanisms. These drugs aim to improve cardiac function and alleviate symptoms.
Understanding Heart Contraction
The heart’s ability to pump blood relies on the precise contraction of its muscle cells, a process driven by the interaction of two main proteins: myosin and actin. These proteins are organized into contractile units called sarcomeres within the muscle fibers. Myosin, often referred to as the “motor protein,” has heads that bind to actin filaments.
This binding initiates a process known as the “power stroke,” where the myosin heads pivot and pull on the actin filaments, causing the muscle to shorten and generate force. Energy from adenosine triphosphate (ATP) is required, which myosin converts into mechanical energy. After the power stroke, a new ATP molecule binds to myosin, allowing it to detach from actin and prepare for the next cycle, enabling the continuous contraction and relaxation of the heart.
How Cardiac Myosin Inhibitors Work
Cardiac myosin inhibitors function by targeting and binding to the cardiac myosin protein. This binding alters the structural state of myosin, making it less likely to interact with actin. These drugs reduce the number of active myosin heads available to form cross-bridges with actin.
This reduction in cross-bridge formation directly decreases the force and frequency of muscle contraction. The inhibitors reduce the heart’s contraction by limiting the energy available for the power stroke. This action helps to reduce the heart’s workload and oxygen demand.
The drugs achieve this effect by modulating the ATPase activity of myosin, the enzyme responsible for converting chemical energy into mechanical energy. By inhibiting this activity, cardiac myosin inhibitors promote a more relaxed state of the heart muscle. This leads to a reduction in abnormal muscle contraction and improved relaxation.
Treating Hypertrophic Cardiomyopathy
Cardiac myosin inhibitors are primarily used to treat hypertrophic cardiomyopathy (HCM), a genetic heart disorder characterized by an abnormal thickening of the heart muscle walls, particularly in the left ventricle. This thickening can obstruct blood flow out of the heart and impair its ability to relax and fill with blood. Patients with HCM often experience symptoms like shortness of breath, chest pain, and fatigue, sometimes even leading to fainting or sudden cardiac death.
In HCM, the heart muscle’s myosin activity is often dysregulated, leading to hypercontractility, meaning the heart squeezes too hard. This excessive contraction contributes to muscle thickening and impaired relaxation. Cardiac myosin inhibitors directly address this issue by reducing hypercontractility and improving the heart’s ability to relax and fill with blood.
Mavacamten (Camzyos) is one such medication that binds to myosin, reducing its contractile force and decreasing hypertrophy. Another example is Aficamten, a newer cardiac myosin inhibitor. Both Mavacamten and Aficamten have shown promising results in reducing left ventricular outflow tract obstruction and improving symptoms in clinical trials.
Patient Outcomes and Safety
Treatment with cardiac myosin inhibitors like Mavacamten and Aficamten has led to significant improvements for patients with obstructive hypertrophic cardiomyopathy. Patients often experience a reduction in symptoms such as shortness of breath and chest pain, alongside an improved capacity for exercise. These medications can also reduce the need for more invasive procedures, such as surgical reduction of the thickened heart muscle.
While generally well-tolerated, these medications require careful medical supervision due to potential side effects. A notable concern is the possibility of a reduction in left ventricular ejection fraction (LVEF), which indicates the heart’s pumping ability. This reduction could potentially lead to heart failure, requiring careful management.
Regular monitoring, typically involving echocardiograms, is necessary to assess LVEF and ensure the medication’s safety and effectiveness. Dizziness and syncope have also been reported as common adverse effects. Close monitoring and dose adjustments are necessary, and these medications must be managed by healthcare professionals to optimize benefits and mitigate risks.