An estimated 1 million people in the U.S. have hypertrophic cardiomyopathy—a heart condition also known as HCM—and many don’t know they have the condition until it’s too late. A genetic disease, HCM often goes undetected until someone in the family experiences symptoms, which can range from irregular heart rhythms and stroke to heart failure and death in people of any age. And HCM is the most common cause of sudden cardiac death in young people.

“It’s an autosomal dominant disorder,” says Washington University cardiologist Sharon Cresci, MD. “That means if just one parent has an abnormal genetic variant linked to HCM, there’s a 50-50 chance that the variant will be passed down to a child or be found in a parent or sibling.” Cresci has special expertise in genetics and advanced imaging for HCM and is the associate director of the Washington University Hypertrophic Cardiomyopathy Center.

HCM is characterized by a thickening, or hypertrophy, of the heart muscle. Over time, HCM can cause the heart to stiffen. It also can cause cellular changes that impact electric signals inside the heart and may lead to dangerous heart arrhythmias. In approximately 70% percent of individuals with HCM, the thickened heart muscle causes an obstruction of blood flow as it exits the heart, a phenomenon called left ventricular outflow tract obstruction. This condition is called obstructive HCM.

Treatment options for HCM and obstructive HCM include medication, surgery and—for some—heart transplantation. Additionally, some people treated at the Center may have the option to participate in clinical trials focused on evaluating investigational drugs and other treatments. One such trial has resulted in a newly approved drug for obstructive HCM that offers positive results.

A breakthrough in care

Washington University interventional cardiologist Richard Bach, MD, FACC, and his team had exhausted non-invasive treatments for a patient suffering from HCM. Surgery seemed to be the only remaining option. Until, that is, Bach enrolled the man, who was in his 50s, in a clinical trial evaluating a drug called mavacamten. “He felt dramatically better after taking the drug. And three years later,” Bach says, “he continues to feel well, which has postponed or eliminated his need for surgery or other interventions.”

No longer an investigational drug, mavacamten—also known by its brand name, Camzyos—was approved by the U.S. Food and Drug Administration in 2022 for treatment of obstructive HCM. This approval came after a landmark, multicenter clinical trial found it was an effective treatment option for obstructive HCM. Washington University physicians at Barnes-Jewish Hospital were the first in the region to offer mavacamten to qualified patients.

“It’s a breakthrough therapy,” says Bach, who served as principal investigator for the arm of the study conducted at Washington University. “We were among the 68 medical centers worldwide that participated in clinical trials evaluating the drug. As a result, we now have the experience to identify and treat patients who may benefit from this new medication. And we were the first center in the region and among the first nationwide to be able to offer it.”

Mavacamten, taken orally, reduces the obstruction in the heart caused by HCM. In the international drug trial for this medication, more than half of the patients taking the drug showed complete relief from the outflow tract obstruction. In a second multicenter study, the majority of patients who were being considered for a surgical intervention but first were treated with mavacamten no longer required the invasive procedure.

A precision medication

Mavacamten belongs to a new class of drugs called myosin inhibitors. Inside the heart, two proteins called myosin and actin work in tandem to control heart-muscle contractions allowing the heart to pump blood throughout the body. “Myosin acts like a lever, and actin is like a filament or string,” explains Bach. “Myosin grabs the actin and pushes it back and forth, causing the heart cells to contract.”

People with HCM have an over-abundance of active myosin, which causes the heart to have excessive or “hyperdynamic” contraction. That contraction, coupled with a thickened heart muscle in the outflow tract, contributes to blockage of blood flow. As a result, excessive pressure builds within the heart. Mavacamten inhibits excess myosin activity, allowing the heart to relax; obstruction and pressure are reduced.

“It’s precision medicine in a once-a-day pill,” says Bach. “The key, however, is that patients who are prescribed this drug will need to be closely supervised at an experienced center.”

The FDA, in fact, mandates close supervision. Because mavacamten relaxes heart muscles it can, in rare cases, inhibit the heart’s pumping function. Given this risk, the FDA approved the drug through its Risk Evaluation and Mitigation Strategy (REMS) program. That REMS qualification means that the FDA requires that healthcare providers undergo training and certification to prescribe the drug and monitor its effects. It also requires that patients receive initial and regular follow-up echocardiograms to monitor dosage and heart function.

“An echocardiogram helps us determine the correct dosage because it measures the gradient of extra pressure across the left ventricular outflow tract. That gradient needs to be visualized carefully and interpreted accurately. It requires clinical expertise to properly acquire and interpret the echocardiogram,” Cresci says.

Bach adds: “This new drug gives us an important new treatment option for patients who have failed more traditional medications, such as beta blockers or calcium channel blockers.”

A brighter future

Washington University interventional cardiologist Richard Bach, MD, FACC, who was one of the investigators in the myosin inhibitor clinical trials, already has several patients through the Center who are registered in the FDA’s mavacamten REMS program. He says, “As an interventional cardiologist who sees many HCM patients each year, I’m very happy to have a new oral medication available for treatment. For those who may benefit from this option, it’s a new treatment with great promise to improve not only their symptoms but also their quality of life.”

Referring Patients to the Hypertrophic Cardiomyopathy Center

The Washington University Hypertrophic Cardiomyopathy Center is accredited by the National Hypertrophic Cardiomyopathy Association and has a dedicated multidisciplinary team of HCM specialists, including cardiologists, genetic cardiologists, electrophysiologists and cardiothoracic surgeons, as well as a team of experienced imaging specialists and nurses. Services include:

• Genetic testing
• Advanced cardiac imaging
• Electrophysiology evaluations
• Medical, non-surgical and surgical interventions
• Athlete screenings
• Counseling

To refer a patient to the center, call: 314-362-1963.