Barnes-Jewish Hospital | Washington University Physicians
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Originally published Oct 2022

By Stephanie Stemmler

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.

New Drug Positive Results for Hypertrophic Cardiomyopathy

“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 affect the heart’s electrical signals, which may lead to dangerous heart arrhythmias. In approximately 70% of people with HCM, the thickened heart muscle causes an obstruction of blood flow as it exits the heart, a phenomenon known as 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.

New treatment for HCM

Washington University 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.”

Cardiologists Sharon Cresci, MD, (left) and Richard Bach, MD, FACC, (right) discuss treatment options with a patient. Photo by Gregg Goldman
Cardiologists Sharon Cresci, MD, (left) and Richard Bach, MD, FACC, (right) discuss treatment options with a patient.
Photo by Gregg Goldman

No longer an investigational drug, mavacamten—also known by its brand name, Camzyos—was approved by the U.S. Food & 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. “We were among the 68 medical centers worldwide that participated in clinical trials evaluating the drug,” says Bach, who served as principal investigator of the study conducted at Washington University. “As a result, we now have the experience to identify and treat patients who may benefit from this new medication.”

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 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.

Targeting the problem

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 specifically targets myosin, inhibiting that protein so the heart can relax; obstruction and pressure are reduced.

“This is 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 muscle, 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. The REMS qualification means the FDA requires that health-care providers undergo training and certification before they can prescribe the drug—and must 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.”

More treatment options

In addition to mavacamten, the Hypertrophic Cardiomyopathy Center offers people with HCM a range of medical, interventional and surgical options. Surgery to treat obstructive HCM works by thinning the thickened heart muscle. This treatment, first available in the 1960s, has been the standard of care for more than 20 years. Washington University cardiothoracic surgeons Ralph Damiano Jr., MD, and Kunal Kotkar, MD, specialize in this surgical procedure, called septal myectomy. A newer, less invasive treatment, called mini-sternotomy, is another option and may offer some people a speedier recovery.

“The incision used in a mini-sternotomy is less than half the length of that required for traditional septal myectomy,” notes Kotkar. “But both procedures can offer good outcomes.” Kotkar also specializes in a more complex procedure called apical myectomy, available at the Washington University and Barnes-Jewish Heart & Vascular Center and at only a few other centers in the U.S. “Some patients with HCM have an obstruction inside one of the lower chambers of the heart,” Kotkar says, “so we work inside the ventricle to remove the blockage and create a larger cavity for blood flow.”

A less invasive procedure called alcohol septal ablation is an option for people who can’t have surgery. In alcohol septal ablation, Bach says, “we use a balloon catheter to block the septal artery that moves blood into the area of thickened muscle.” Once the balloon is in place, alcohol is injected into the area, which destroys the thickened tissue. “As a result, some of the obstruction is relieved almost immediately, and, as the treated area heals, the septum is thinned without requiring open-heart surgery,” Bach adds.

HCM also can cause atrial fibrillation, an abnormal heart rhythm that may lead to heart failure if untreated. In 1987, James Cox, MD, former chief of cardiothoracic surgery at Washington University, and colleagues developed what’s now known as the Cox-Maze procedure. During Cox-Maze surgery, specialists create a series of tiny incisions in the heart that block abnormal electrical signals.

Since then, Damiano has introduced less invasive advances to this procedure that have further improved outcomes for patients. He also performs a combined treatment that includes septal myectomy and a modified Cox-Maze procedure to treat HCM and atrial fibrillation simultaneously.

Not all people with HCM develop obstruction. For people with non-obstructive HCM, treatment includes medication and, for those who aren’t helped by medication, heart transplantation. Physician-researchers at the Hypertrophic Cardiomyopathy Center are involved in clinical trials evaluating new medications to treat non-obstructive HCM, and they collaborate closely with the Washington University and Barnes-Jewish Transplant Center to care for people needing transplantation.

HCM and genetic testing

An inherited disease, HCM can run in families—and it can develop at any age. In many instances, HCM is undiagnosed until a significant heart problem occurs. When that happens, genetic testing for the patient and the immediate family can help to clarify the cause of symptoms and offer care options for others in the family who may be at risk. Screening often includes an echocardiogram as well.

Cresci says, “We can identify whether other family members carry a disease-causing genetic variant of HCM before the disease develops.” She notes that the decision to undergo screening should be a shared decision among family members. “We work with the family so they understand the genetic nature of the disease and the possible implications of any test results.”

Currently, Cresci and colleagues are engaged in research to better diagnose and understand HCM. She is the principal investigator of an ongoing Washington University observational study that to date has enrolled more than 1,000 patients and family members. The aim is to better identify markers of the onset, progression and prognosis of HCM, as well as to identify other disease-associated genetic variants.

A brighter future

Bach, who was one of the investigators in the myosin inhibitor clinical trials, has several patients being treated at the Hypertrophic Cardiomyopathy 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.”

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