Hypertrophic cardiomyopathy (HCM) is a condition characterized by the abnormal thickening of the heart muscle, most often affecting the walls of the left ventricle and the septum that separates the heart’s chambers. This thickening makes the heart stiff and impairs its ability to fill with blood effectively, leading to symptoms like shortness of breath, chest pain, and fatigue. For the most common, genetic form of the disease, a complete return to a normal heart structure is not currently possible. However, modern medicine offers highly effective treatments that can manage symptoms, prevent serious complications, and, in some cases, structurally improve the heart’s function.
The Underlying Cause of Hypertrophy
The primary reason the heart muscle thickens in most HCM cases is rooted in genetics, specifically mutations within the genes that code for the heart’s contractile proteins. These proteins form the sarcomere, the basic functional unit of the muscle cell responsible for contraction. The most frequently implicated genes are MYH7 and MYBPC3, which account for approximately 40% of all HCM cases.
These mutations lead to a fundamental defect in the sarcomere, causing the muscle to contract with excessive force and use energy inefficiently. The cardiac muscle cells (myocytes) respond by enlarging and becoming disorganized, a condition known as myocyte disarray. This structural chaos makes the left ventricular wall abnormally stiff, resulting in diastolic dysfunction where the heart struggles to relax and fill with blood. In many patients, this thickening creates a mechanical obstruction to blood flow leaving the heart, known as left ventricular outflow tract obstruction.
Standard Pharmacological Management
Drug treatments for HCM primarily control symptoms and manage mechanical problems, rather than reversing the muscle thickness itself. Beta-blockers are the most widely used first-line agents because they slow the heart rate and reduce the force of muscle contraction. This allows more time for the left ventricle to fill with blood and lessens any obstruction. Non-dihydropyridine calcium channel blockers, such as verapamil or diltiazem, function similarly by improving diastolic relaxation and reducing heart contractility, offering an alternative for patients who cannot tolerate beta-blockers.
For patients whose symptoms persist, an antiarrhythmic agent like disopyramide may be added. Disopyramide is a potent negative inotrope, meaning it further decreases the force of contraction, which is effective at reducing the outflow tract obstruction. Because HCM is associated with an increased risk of atrial fibrillation, many patients also require anticoagulants to prevent stroke. These established medications are crucial for improving quality of life and reducing complications, but they do not address the underlying genetic cause or shrink the muscle back to a normal size.
Interventional Procedures for Structural Relief
When medication fails to adequately control symptoms or reduce a significant outflow tract obstruction, interventional procedures provide immediate structural relief. These procedures physically modify the heart muscle to ease the blockage, but they do not cure the underlying genetic disorder.
The gold standard surgical option is Septal Myectomy, an open-heart surgery where a cardiac surgeon precisely removes a small amount of the thickened septum that is obstructing blood flow. This removal of excess muscle tissue offers a highly effective, immediate, and durable solution for the obstruction and associated symptoms.
A less invasive, catheter-based alternative is Alcohol Septal Ablation (ASA), often favored for elderly patients or those with high surgical risk. This procedure involves injecting pure alcohol into the coronary artery branch that supplies blood to the obstructing septum. The alcohol causes a controlled, localized heart attack, leading to the death of the targeted muscle tissue, which shrinks and scars, thereby reducing the obstruction.
For patients at high risk of sudden cardiac death, an Implantable Cardioverter-Defibrillator (ICD) may be placed. This device constantly monitors the heart rhythm and delivers an electrical shock to restore a normal heartbeat if a life-threatening arrhythmia occurs.
Emerging Therapies Targeting Structural Change
The most recent advances involve novel therapies that directly target the disease mechanism at the molecular level. These emerging compounds are the closest medical science has come to inducing a form of structural improvement in the heart. The first-in-class example is mavacamten, a cardiac myosin inhibitor that works by reducing the excessive cross-bridging between the muscle’s actin and myosin filaments.
By reducing the number of myosin heads that can engage in contraction, mavacamten normalizes the hypercontractility characteristic of the disease. This targeted action effectively reduces the left ventricular outflow tract obstruction and has shown promise in reducing the need for invasive septal reduction therapies.
Clinical trials have demonstrated that this molecular modulation improves patients’ functional capacity and symptoms. This represents a significant shift from non-specific symptom control to a therapy that addresses the fundamental mechanism of the disease. Other similar compounds, such as aficamten, are also being developed to modulate the sarcomere, reduce hypercontractility, and potentially lead to sustained structural and functional benefits.