A change of heart -- new drug for HCM reduces heart mass

November 16, 2020

For the first time, a medication has impacted heart muscle thickness and function for patients with the most common inherited heart condition, rather than simply addressing their symptoms.

"This is the first study to show a favorable impact of a medication on cardiac structure and function in any form of hypertrophic cardiomyopathy," says Sara Saberi, M.D., an assistant professor of internal medicine and a cardiologist at the Michigan Medicine Frankel Cardiovascular Center.

Current options, Saberi explains, might help patients feel better today, but they don't help them live longer, nor do they prevent people from experiencing heart failure down the road. They also don't affect any of the heart structural abnormalities that define the disease: thickness of the heart muscle, resultant stiffness and abnormalities in other cardiac structures.

"There's a huge void. HCM is a chronic progressive disease that still does not have a cure," Saberi says.

She presented the results of her team's EXPLORER-HCM CMR sub-study at the 2020 American Heart Association Scientific Sessions, which published simultaneously in Circulation.

Addressing the underlying cause of HCM

In HCM, the motor proteins interact with each other too much, causing over-vigorous squeeze of the muscle and causing stiffness of the muscle.

A medication designed specifically for HCM, mavacamten, is currently being studied in a variety of clinical trials. It's part of a new class of drugs called cardiac myosin inhibitors. The medication works by blocking a protein called myosin from interacting too much with other motor proteins, which then allows the heart muscle to squeeze and relax more normally, Saberi explains. It is effective at reducing obstruction to blood flow within the heart that can occur with the disease.

"It's the first class of medications that actually targets the underlying pathophysiology of HCM."

The primary measure for this study, the mass of the heart, was significantly reduced in those patients taking the drug as opposed to those taking placebo, Saberi says.

In September, Saberi and colleagues published findings from the EXPLORER-HCM randomized controlled trial in The Lancet. The patients had significant improvements in obstruction to blood flow in the heart and said they felt better after taking the drug for 30 weeks. They showed improvements in markers like exercise capacity. Now, this substudy explores some of the reason why people may be feeling better, Saberi says.

Results from cardiac imaging

The substudy was done using imaging of the study participants' hearts.

"Cardiac MRI has such incredible visual and spatial resolution that you can accurately examine the heart's mass, volume, ejection fraction, or how well the blood is pumping, and fibrosis, which is the scar burden in the heart muscle," Saberi says.

Her team observed these encouraging results after just 30 weeks of treatment, which would be a plus for patients, Saberi says.

"It's also encouraging that we don't see a worsening in fibrosis along with the normalization in ejection fraction," she says. Patients originally had a very high ejection fraction, but after treatment it moved into the normal range.

Although HCM is considered a rare disease, it affects about one in 500 people, Saberi says, so there's a large need for more effective therapeutics.

The EXPLORER-HCM trial was a phase three trial that studied the use of mavacamten in obstructive HCM, and has moved into a five-year open-label extension. A concurrent phase two trial, MAVERICK-HCM, investigated safety and tolerability in non-obstructive HCM. Those participants are also in the five-year open-label extension study now. Saberi says a phase three trial that would look at how well it works for those patients with non-obstructive HCM would be the next step.

The medication is not currently available outside of a clinical trial setting, Saberi says.
-end-
Paper cited: "Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM CMR substudy analysis," Circulation. DOI: CIRCULATIONAHA/2020/052359DR1

Disclosure: MyoKardia Inc., the company that makes investigational drug mavacamten, funded the research and paid consulting fees to Saberi and other investigators.

Michigan Medicine - University of Michigan

Related Blood Flow Articles from Brightsurf:

Brain regions with impaired blood flow have higher tau levels
In Alzheimer's disease, impaired blood flow to brain regions coincides with tau protein buildup.

3D ultrasound enables accurate, noninvasive measurements of blood flow
A 3D ultrasound system provides an effective, noninvasive way to estimate blood flow that retains its accuracy across different equipment, operators and facilities, according to a new study.

Blood flow recovers faster than brain in micro strokes
Work by a Rice neurobiologist shows that increased blood flow to the brain is not an accurate indicator of neuronal recovery after a microscopic stroke.

Exercise improves memory, boosts blood flow to brain
Scientists have collected plenty of evidence linking exercise to brain health, with some research suggesting fitness may even improve memory.

3D VR blood flow to improve cardiovascular care
Biomedical engineers are developing a massive fluid dynamics simulator that can model blood flow through the full human arterial system at subcellular resolution.

MRI shows blood flow differs in men and women
Healthy men and women have different blood flow characteristics in their hearts, according to a new study.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Blood flow monitor could save lives
A tiny fibre-optic sensor has the potential to save lives in open heart surgery, and even during surgery on pre-term babies.

Changes in blood flow tell heart cells to regenerate
Altered blood flow resulting from heart injury switches on a communication cascade that reprograms heart cells and leads to heart regeneration in zebrafish.

Blood flow command center discovered in the brain
An international team of researchers has discovered a group of cells in the brain that may function as a 'master-controller' for the cardiovascular system, orchestrating the control of blood flow to different parts of the body.

Read More: Blood Flow News and Blood Flow Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.