On October 22, patients, physicians, and other interested parties will have the opportunity to provide input on the value and cost of mavacamten – the first drug specifically designed to treat hypertrophic cardiomyopathy.
Editor’s note: You have probably noticed a distinct uptick in clinical trials of potential treatments for hypertrophic cardiomyopathy. HCMBeat has been following this trend and has previously published a host of stories about such trials, including this story about the positive results from the REDWOOD-HCM Phase 2 clinical trial, as well as past stories discussing the biopharmaceutical company Cytokinetics, its drug aficamten (previously known as CK-274), and the REDWOOD-HCM trial.
Some of these earlier stories are as follows:
Recently, Cynthia Waldman of HCMBeat had the opportunity to speak over Zoom with Dr. Martin Maron, who recently served as the principal investigator of Cytokinetics’ REDWOOD trial. The conversation focused both on Cytokinetic’s drug aficamten (previously known as CK-274), and the new class of drugs known as “myosin inhibitors.” What follows is a transcript of their conversation (which has been edited for readability).
Recent HCM research has taken a much needed pivot away from a focus on adult men to the exclusion of others. Women and babies get HCM too, yet until this point, there has been far less attention and research on their issues. HCM is not just a disease of adult men, though they do make up the majority of participants in research studies which inform current treatment protocols.
Finally that may be changing. It seems that people are finally starting to pay some attention to other folks who have HCM. Here is a recent European article looking at HCM in infants and here is a recent article looking at HCM in women.
Let’s hope the trend continues since previous research has shown that HCM is often more severe in these two groups.
A new technology called “virtual native enhancement” (VNE) may soon eliminate the need for gadolinium as a contrast agent for patients with hypertrophic cardiomyopathy undergoing cardiac MRI. Gadolinium, a heavy metal contrast agent which is injected intravenously, has long been used in cardiac MRI scans to spot cardiac scar tissue in patients with HCM. In 2017, the FDA issued a safety communication relating to gadolinium because it was found that gadolinium remains in the body for months to years after the use of the drug.
The new VNE technology, recently described in the journal Circulation, uses artificial intelligence (AI) to virtually enhance the standard MRI image. The technology was developed using data taken from 1348 HCM patients and was validated in the HCM population, but the technology may have uses extending beyond HCM.
By avoiding the use of the contrast agent, this technology avoids side effects and long term consequences from the use of gadolinium. Additionally, it will make cardiac MRI available to patients who are allergic to gadolinium. VNE is also faster and cheaper that current technology used for cardiac MRI, which may make more frequent MRI monitoring of patients feasible.
A common cardiac drug called valsartan has shown positive results in those who carry the gene for hypertrophic cardiomyopathy but who do not have overt disease.
As reported by Dr. Carolyn Ho of Brigham and Women’s Hospital and Harvard Medical School at the online European Society of Cardiology meeting, the Phase 2 double blind VANISH trial looked at 178 pre-symptomatic young people who carried a sarcomere gene mutation known to cause HCM. These patients were randomly assigned to take either valsartan, an angiotensin II receptor blocker (ARB), or a placebo.
At the time of trial enrollment, these patients showed no or only mild signs of the disease. At the end of the two year trial, the individuals who took valsartan had a better overall cardiac picture compared to the group taking only the placebo.
Dr. Ho had this to say in a story about the trial results in Mirage News:
“Valsartan improved cardiac structure/function and remodeling in patients with early stage sarcomeric HCM, suggesting that this strategy may help prevent disease progression among those who have received a genetic diagnosis of HCM.”
“Our results suggest that valsartan may not only stabilize disease progression but may also promote improvement.”
You can also read this summary of the presentation on MedPage Today.
A study by researchers from Mayo Clinic recently published in the International Journal of Cardiology found that a deep learning artificial intelligence algorithm using a standard 12 lead electrocardiogram was able to detect hypertrophic cardiomyopathy in young people with impressive accuracy. This accuracy was particularly strong among adolescents aged 15 – 18.
Mayo has been looking at artificial intelligence for its potential to screen populations for HCM for some time now. Here is a previous HCMBeat story about Mayo’s work on artificial intelligence from February 2020.
The July edition of the the American College of Cardiology’s magazine features a cover story about HCM.
The article surveys the history of HCM and then moves through the evolution into contemporary treatments. The article also contains a summary of important topics from the new 2020 AHA/ACC Guidelines and highlights EXPLORER-HCM, the recent groundbreaking clinical trial of mavacamten.
Check it out when you can.
Many HCM patients, perhaps even the majority, are currently unable to identify the specific gene behind their HCM through genetic testing. Despite this obvious difference, family screening, risk stratification and treatment standards are no different for patients who carry a HCM gene and those who do not have identified gene(s).
In particular, non-sarcomere positive patients:
- have a better prognosis, with lower rates of heart failure, sudden death, atrial fibrillation and stroke
- Have lower incidence of family members affected by the disease
- Are more likely to have additional medical conditions such as obesity, hypertension and diabetes
The article by Dr. Hugh Watkins, a British HCM and genetic expert, suggests that:
- the risk to first degree relatives of this type of HCM patient is less than 50% and therefore, there is less need for repeated screening of relatives
- Hypertension should be treated more aggressively in these patients.
Today it has been 15 years since my septal myectomy at Mayo Clinic!
Watch the video or read the transcript of Dr. Steve Ommen’s recent interview on Medscape.
In this interview, he discusses the recent AHA/ACC treatment guidelines for hypertrophic cardiomyopathy (HCM), his thoughts about the new HCM drug mavacamten, and the importance of collaboration between your local care team and the team at a HCM specialty center.
Although the gene positive individuals lacked the characteristic left ventricular wall thickening of HCM, 1 of 5 patients who carried the HCM gene showed marked regional perfusion defects when compared to healthy individuals. Hence, the researchers concluded that a person who is gene positive for the disease may show reduced cardiac perfusion before they develop hypertrophy.
The study compared 50 patients who carried the HCM gene but had no signs of left ventricular hypertrophy to 28 healthy individuals. Both groups underwent Cardiac MRI testing.
The researchers theorize that perfusion mapping may be a useful way to identify HCM gene carriers who will go on to develop the disease.